In 2004 and 2014,two monographs on hypobaric storage(LP)were published by Stanley P.Burg.Based on his theoretical framework and technological advancements,as well as the research and development of equipment conducted...In 2004 and 2014,two monographs on hypobaric storage(LP)were published by Stanley P.Burg.Based on his theoretical framework and technological advancements,as well as the research and development of equipment conducted under his guidance,alongside customer practices and reflections on various scientific literature both domestically and internationally,it is posited that,as articulated in the monograph,misconceptions regarding his theory and technology in Western scientific literature prior to 1985 continue to persist.This ongoing dissemination of misunderstandings has resulted in a near stagnation of research and has adversely impacted the Chinese academic community as well.Consequently,it is essential to delineate the characteristics and main points of its theory and technology,with the aim of offering guidance to individuals seeking to comprehend its foundational purpose.LP technology is a dynamic physical technology that continuously and uninterruptedly extracts air from a closed container and simultaneously introduces fresh,low-pressure moist air from the external environment,while maintaining specific levels of humidity and/or temperature within the container and upholding a predetermined pressure value.Preservation technology is the collective term for the set of various technical parameters associated with preservation,including pressure,relative humidity,and other relevant factors,to which LP equipment is specifically designed.The theory of LP is characterized by the enhanced diffusion of gases and vapors that enter and exit the commodity in a dynamic manner under low pressure conditions.The theoretical points involve equipment performance,low pressure,the impact of trace concentrations of gases such as O_(2),CO_(2) and C_(2)H_(4) that naturally occur at low pressure,diffusive mass transfer,heat transfer,and impacts on the activity of enzymes associated with maturation and senescence.The technology is characterized by dynamic low pressure,and the range of commodities preserved is comparable to that of refrigeration.However,certain commodities exiting the hypobaric environment possess subsequent preservation advantages that are not available through refrigeration.The main points of the technology encompass an extended sotrage life,a postponement of quality degradation,minimized water loss,the suppression of pathogen growth,and the killing of both internal and external insects of the commodity under dynamic low pressure conditions.The core advantage of LP technology lies in its ability to significantly reduce water loss,inhibit respiration and C_(2)H_(4) action,and pathogen growth,killing insects and modulate the activity of enzymes associated with maturation and senescence in post-harvest fresh horticultural products.Consequently,this technology plays a crucial role in prolonging the post-harvest lifespan of these commodities and mitigating quality degradation.Over the past decade,researchers in China have developed a hypobaric short period treatment technology,grounded in LP theory and technical practice,which is commonly referred to as hypobaric treatment.This method has garnered significant attention,leading to an increase in both domestic and international research.A growing body of literature categorizes LP as hypobaric treatment,while some studies also consider vacuum packaging and modified atmosphere packaging(MAP)as LP or hypobaric treatment.Misunderstandings are exacerbated by confusion surrounding nomenclature,which,in conjunction with pre-existing misconceptions,represents a significant barrier to both the research and practical application of the technology.The successful commercial implementation of a vacuum cold fresh chain,centered on LP or hypobaric treatment technology,may be the sole solution to the prevailing misunderstandings associated with LP.展开更多
AIM: To investigate the protective effect of glutamine (Gln) on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.
Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
Chronic intermittent hypobaric hypoxia (CIHH) is a treatment of moderate hypoxia that simulates high altitude interrupted by normoxia. Growing evidence shows that CIHH has multiple beneficial effects on
In recent ten years in China,the application research of hypobaric storage was extended to the non-freeze preservation of cooked food,fresh-cut vegetables,edible fungi and fruits,preliminary processing of growing area...In recent ten years in China,the application research of hypobaric storage was extended to the non-freeze preservation of cooked food,fresh-cut vegetables,edible fungi and fruits,preliminary processing of growing area and vacuum cold fresh chain to the cold chain breakage for horticultural products,and also to the investigation of principle and theory but the investigation results would have some evident difference. This paper will simply summarize the basic conception,principle,two withdrawing air type hypobaric storage technologies,and introduce many examples as mentioned above extending in China. This paper thinks that the master mechanism of preservation of LP for fresh horticultural products effectively inhibits the activity change of manifold enzymes,which are PAL,POD,PPO,CAT,CAD,SOD et al.,affecting the maturation and caducity of fresh horticultural products during LP storage for a short period,as a result,to reduce both risk of physiology obstacle and disease and to prolong their postharvest life; for the foreseeable future Burg's hypobaric storage technology and hypobaric short period treatment technology will play an important role in the preservation on fresh agricultural products and food preservation in storage and transportation,the preliminary processing of growing area,fresh logistics,establishing the operating platform of perishable food and high business value,fresh e-business,and fresh delivery for scattered families,establishing the operating platform of fresh-cut vegetables including edible fungi and so on in China or in the world.展开更多
Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.T...Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.展开更多
Effects of hypobaric storage on physiological and biochemical changes in Dong jujube fruit were investigated. Hypobaric storage significantly delayed the decrease in firmness and maintained content of ascorbic acid, r...Effects of hypobaric storage on physiological and biochemical changes in Dong jujube fruit were investigated. Hypobaric storage significantly delayed the decrease in firmness and maintained content of ascorbic acid, reduced accumulation of ethanol and acetaldehyde in pulp and respiration, inhibited activities of ascorbic acid oxidase and alcohol dehydrogenase and slowed down the rate of ethylene production, but had little effect on flesh browning of the fruit.展开更多
Objective：To investigate the characteristics of fat metabolism in rat skeletal muscle after hypobaric hypoxia acclimation. Methods： Sprague-Dawley rats were divided into 3 groups randomly： control group （H0）, hyp...Objective：To investigate the characteristics of fat metabolism in rat skeletal muscle after hypobaric hypoxia acclimation. Methods： Sprague-Dawley rats were divided into 3 groups randomly： control group （H0）, hypoxic 5-day group （HS）, and hypoxic 15-day group （H15）. Animals of H5 and 15 groups were exposed to hypobaric hypoxia chamber simulating 5 000 m high altitude for 5 d or 15 d respectively, 23 h per day. H0 group stayed outside of chamber The level of fatty acid oxidation and uptake, and glucose oxidation were examined, and the level of non-esterified fatty acids （NEFA）, ATP and phosphocreatine （PCr） were also assayed in rat skeletal muscles. Results： The contents of ATP and PCr in H5 group were lower than those in H0 and H15 groups （P〈0.05）, while there was no significant difference between H0 and H15. Compared with H0, the blood NEFA level in all hypoxia groups was increased significantly （P〈0.05）. The muscle NEFA level in H15 group was greatly higher than that in H0 and H5 groups. The rates of fatty acid oxidation and uptake in H15 group were significantly higher than those in H0 and H5 groups （P〈0.05）, and the rate of glucose oxidation in all hypoxia groups was significantly decreased than that in H0 group （P〈0.05）. Conclusion： It is concluded that the enhanced fat oxidation may be one of the mechanisms in the maintenance of energy homeostasis after hypobaric hypoxic acclimation.展开更多
Objective The hypersensitivity of the kidney makes it susceptible to hypoxia injury.The involvement of neutrophil extracellular traps(NETs)in renal injury resulting from hypobaric hypoxia(HH)has not been reported.In t...Objective The hypersensitivity of the kidney makes it susceptible to hypoxia injury.The involvement of neutrophil extracellular traps(NETs)in renal injury resulting from hypobaric hypoxia(HH)has not been reported.In this study,we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism.Methods A total of 24 SD male rats were divided into three groups(n=8 each):normal control group,hypoxia group and hypoxia+pyrrolidine dithiocarbamate(PDTC)group.Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters(oxygen partial pressure about 6.9 kPa)for 7 days.PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days.Pathological changes of the rat renal tissues were observed under a light microscope;the levels of serum creatinine(SCr),blood urea nitrogen(BUN),cell-free DNA(cf-DNA)and reactive oxygen species(ROS)were measured;the expression levels of myeloperoxidase(MPO),citrullinated histone H3(cit-H3),B-cell lymphoma 2(Bcl-2),Bax,nuclear factor kappa B(NF-κB)p65 and phospho-NF-κB p65(p-NF-κB p65)in rat renal tissues were detected by qRT-qPCR and Western blotting;the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining.Results After hypoxia,the expression of NF-κB protein in renal tissues was significantly increased,the levels of SCr,BUN,cf-DNA and ROS in serum were significantly increased,the formation of NETs in renal tissues was significantly increased,and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues.When PDTC was used to inhibit NF-κB activation,NETs formation in renal tissue was significantly decreased,the expression level of Bcl-2 in renal tissues was significantly increased,the expression level of Bax was significantly decreased,and renal injury was significantly alleviated.Conclusion HH induces the formation of NETs through the NF-κB signaling pathway,and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.展开更多
To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats wer...To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.展开更多
Chronic exposure to hypobaric hypoxia (HH) causes memory impairment and prolonged state of mental confusion. However, effect of high altitude exposure on mood state and its underlying mechanisms have been poorly studi...Chronic exposure to hypobaric hypoxia (HH) causes memory impairment and prolonged state of mental confusion. However, effect of high altitude exposure on mood state and its underlying mechanisms have been poorly studied.? Present study was undertaken to investigate the mood state alteration following chronic exposure to HH. Male Sprague Dawley rats were divided into five groups and exposed to hypoxia for 3, 7, 14 and 21 days in an animal decompression chamber at an altitude of 25,000ft. Anxiety-and depression-like behaviors were assessed by using various mazes along with changes in serotonin and glutamate level. Our study revealed a decrease in exploratory, grooming and rearing behavior in open field test following initial exposure to HH for 7 days without affecting the locomotory behavior. Initial exposure to HH-decreased time spent in open arm of elevated plus maze indicating induction of anxiety-like behavior which normalized on prolonged hypoxic exposure for 21 days. Hypoxic exposure for 7 days induced anhedonia and increased despair behavior in rat while there was steady improvement in these behaviors when exposed for 21 days. Decrease in serotonin level was noted in hippocampus along with elevated corticosterone and glutamate level which gradually decreased on prolonged exposure to HH. These findings suggest that initial exposure to HH increases transient anxiety-like behavior in rats followed by gradual improvement in mood state on prolonged exposure. Further, the study also indicates the involvement of serotonergic system in mood state alteration at high altitude following chronic exposure and reoxygenation.展开更多
The exploration of the effects of pressure leads to new insights into the mycelial growth of Paecilomyces hepiali fungal strain. This strain has been generally accepted as true anamorph of wild Ophiocordyceps sinensis...The exploration of the effects of pressure leads to new insights into the mycelial growth of Paecilomyces hepiali fungal strain. This strain has been generally accepted as true anamorph of wild Ophiocordyceps sinensis. It is only found at high altitude area like Himalayan plateau where atmospheric pressure is very low. Most of researches about P. hepiali and artificial mycelial cultivation have been done around mean sea level pressure. Then new experimental set up was developed and described. The apparatus permitted growth of mycelia under different pressure levels while other micro environmental conditions were carefully controlled. Potato dextrose broth was used as liquid media. As solid and semi solid media, sorghum base media and potato dextrose agar were prepared. Results of mycelial growth under hypobaric pressures and hyperbaric pressure were compared with mycelial growth of atmospheric pressure and hence growth influence has been shown. Specially, -100 mmHg treated sample showed significantly highest growth in both solid media and semi solid media. In semi solid media, -100 mmHg was not significant with other reduced pressure treatments. Meanwhile, -150 mmHg treated samples showed significantly highest mycelial growth of liquid media and -150 mmHg of pressure adversely affected on water contents of solid growing media. This may be an effect of pressure on enzymatic activities, protein and fatty acid of plasma membrane. As well as, pressure changes equilibrium of biochemical reactions, bond of some molecules and partial pressure of air molecules. Further molecular and biochemical researches are required to evaluate the possible stimulation of mycelial growth through hypobaric and hyperbaric treatments.展开更多
Objective:To study the effects of dexmedetomidine combined with hypobaric lumbar anesthesia on pain mediator secretion as well as inflammatory response and stress response activation in elderly patients with hip repla...Objective:To study the effects of dexmedetomidine combined with hypobaric lumbar anesthesia on pain mediator secretion as well as inflammatory response and stress response activation in elderly patients with hip replacement.Methods: Elderly patients who were>70 years old and underwent hip replacement in Hancheng People's Hospital between March 2015 and June 2017 were chosen and randomly divided into the experimental group who accepted dexmedetomidine combined with hypobaric lumbar anesthesia and the control group who accepted hypobaric lumbar anesthesia alone. The levels of pain mediators and stress mediators in serum as well as the expression of inflammatory molecules in peripheral blood were measured before surgery, the same day after surgery and 3 d after surgery.Results:Compared with those of same group before surgery, CGRP,β-EP, SP, BK, TNF-α, ACTH, F-C, F-Ins, NE and MDA levels in serum as well as NLRP3, Caspase-1, TLR4 and NF-κB mRNA expression in peripheral blood of both groups significantly increased the same day after surgery and 3 d after surgery, and CGRP,β-EP, SP, BK, TNF-α, ACTH, F-C, F-Ins, NE and MDA levels in serum as well as NLRP3, Caspase-1, TLR4 and NF-κB mRNA expression in peripheral blood of experimental group the same day after surgery and 3 d after surgery were significantly lower than those of control group.Conclusion: Dexmedetomidine combined with hypobaric lumbar anesthesia for hip replacement in the elderly can reduce the secretion of pain mediators and relieve the inflammatory response and stress response.展开更多
Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD...Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.展开更多
Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness.Autophagy plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains unknown.Here we used an HH cham...Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness.Autophagy plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains unknown.Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain damage.The autophagic agonist rapamycin only promotes the initiation of autophagy.By proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic flux.Overexpression of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with rapamycin.Furthermore,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure.These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.展开更多
Chronic intermittent hypobaric hypoxia(CIHH)is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension(RVH). In this study, RVH was in...Chronic intermittent hypobaric hypoxia(CIHH)is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension(RVH). In this study, RVH was induced by the 2-kidney-1-clip method(2 K1 C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure(ABP), heart rate(HR), and renal sympathetic nerve activity(RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii(NTS) in anesthetized rats.Evoked excitatory postsynaptic currents(eEPSCs) and spontaneous EPSCs(sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase(nNOS) and endothelial NOS(eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHHtreated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and e NOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via upregulating NOS expression in the NTS.展开更多
The gut microbiota is involved in host responses to high altitude.However,the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood.Here,we used a rat model of h...The gut microbiota is involved in host responses to high altitude.However,the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood.Here,we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome,short-chain fatty acids(SCFAs),and bile acids(BAs)over 28 d.We identified weight loss,polycythemia,and pathological cardiac hypertrophy in hypoxic rats,accompanied by a large compositional shift in the gut microbiota,which is mainly driven by the bacterial families of Prevotellaceae,Porphyromonadaceae,and Streptococcaceae.The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides,Alistipes,and Lactococcus genera and a larger Bacteroides to Prevotella ratio.Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces,suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge.Interestingly,the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota,partially inhibited the increased abundance of the Bacteroides and Alistipes genera,restored the decrease of plasma propionate,and moderately ameliorated cardiac hypertrophy in hypoxic rats.Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge.Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.展开更多
Dear Editor,Myocardial injury following ischemia/reperfusion(I/R)is a common clinical scenario in patients suffering from ischemic heart disease(Hausenloy et al.,2016).The involvement of proteins and signaling pathway...Dear Editor,Myocardial injury following ischemia/reperfusion(I/R)is a common clinical scenario in patients suffering from ischemic heart disease(Hausenloy et al.,2016).The involvement of proteins and signaling pathways is well studied in myocardial I/R injury and protection(Hausenloy et al.,2016;Yang et al.,2012),however,more than 98%of the transcriptional output in mammals are noncoding RNAs(ncRNAs).These products range from short microRNAs(miRNAs)to long noncoding RNAs(lncRNAs,Das et al.,2018)and modulate critical pathophysiologic mechanisms,such as apoptosis,oxidative stress,Ca2+overload and inflammation,during myocardial I/R injury and protection(Das et al.,2018).展开更多
Background:Hypobaric hypoxia(HH)exposure at high altitudes can result in a decline in cognitive function,which may have a serious impact on the daily life of people who migrate to high altitudes.However,the specific H...Background:Hypobaric hypoxia(HH)exposure at high altitudes can result in a decline in cognitive function,which may have a serious impact on the daily life of people who migrate to high altitudes.However,the specific HH-induced changes in brain function remain unclear.This study explored changes in brain activity in rats exposed to a sustained HH environment using functional magnetic resonance imaging(fMRI).Methods:Healthy male rats(8 weeks old)were randomly divided into a model group and a control group.A rat model of cognitive impairment induced by sustainedHHexposure was established.The control and model groups completed training and testing in the Morris water maze(MWM).A two-sample t-test for between-group difference comparisons was performed.Repeated measures analyses of variance for within-group comparisons were performed and post-hoc comparisons were made using the Tukey test.Between-group differences in spontaneous brain activity were assessed using a voxel-wise analysis of resting-state fMRI(rs-fMRI),combined with analyses of the fractional amplitude of low frequency fluctuations(fALFF)in statistical parametric mapping.Results:In the MWM test,the escape latencies of the model group were significantly longer compared with those of the control group(control group vs.model group,day 1:21.6±3.3 s vs.40.5±3.4 s,t=–11.282;day 2:13.5±2.2 s vs.28.7±5.3 s,t=–7.492;day 3:10.5±2.8 s vs.22.6±6.1 s,t=–5.099;day 4:9.7±2.5 s vs.18.6±5.2 s,t=–4.363;day 5:8.8±2.7 s vs.16.7±5.0 s,t=–3.932;all P<0.001).Within both groups,the escape latency at day 5 was significantly shorter than those at other time points(control group:F=57.317,P<0.001;model group:F=50.718,P<0.001).There was no within-group difference in average swimming speed(control group,F=1.162,P=0.956;model group,F=0.091,P=0.880).Within the model group,the time spent within the original platform quadrant was significantly shorter(control group vs.model group:36.1±5.7 s vs.17.8±4.3 s,t=7.249,P<0.001)and the frequency of crossing the original platform quadrant was significantly reduced(control group vs.model group:6.4±1.9 s vs.2.0±0.8 s,t=6.037,P<0.001)compared with the control group.In the rs-fMRI study,compared with the control group,rats in the model group showed widespread reductions in fALFF values throughout the brain.Conclusions:The abnormalities in spontaneous brain activity indicated by the fALFF measurements may reflect changes in brain function after HH exposure.This widespread abnormal brain activity may help to explain and to provide new insights into the mechanism underlying the impairment of brain function under sustained exposure to high altitudes.展开更多
Objective To observe pancreatic ER kinase （PERK） signaling of unfolded protein response （UPR）. Methods The rats were divided into control, model, and ginsenoside Rb; （Rbl） groups, and put into hypoxia chamber to...Objective To observe pancreatic ER kinase （PERK） signaling of unfolded protein response （UPR）. Methods The rats were divided into control, model, and ginsenoside Rb; （Rbl） groups, and put into hypoxia chamber to establish the acute plateau stress model. The water solutions of Rbl were given to rats in Rb; group for 7 d. After that, The behavior of rats was observed by Y-maze and passive avoidance test and the rats were sacrificed in a batch for detection by Western blotting. Results Hypobaric hypoxia mediated UPR pathway accompanied the activation of protective pathways such as PERK-elF2a-ATF4 and Grp78/Bip pathways. On the other hand, RbT, the extract from herbal medicine ginseng, increased on the expression of PERK, eIF2a, ATF4, and Grp78/Bip in rats. Conclusion The results indicate that PERK-elF2a-ATF4-GRP78 pathway is a potential target for therapeutic applications in high altitude diseases and Rb] can attenuate the injury to memory function caused by hypobaric hypoxia neurotoxicity.展开更多
文摘In 2004 and 2014,two monographs on hypobaric storage(LP)were published by Stanley P.Burg.Based on his theoretical framework and technological advancements,as well as the research and development of equipment conducted under his guidance,alongside customer practices and reflections on various scientific literature both domestically and internationally,it is posited that,as articulated in the monograph,misconceptions regarding his theory and technology in Western scientific literature prior to 1985 continue to persist.This ongoing dissemination of misunderstandings has resulted in a near stagnation of research and has adversely impacted the Chinese academic community as well.Consequently,it is essential to delineate the characteristics and main points of its theory and technology,with the aim of offering guidance to individuals seeking to comprehend its foundational purpose.LP technology is a dynamic physical technology that continuously and uninterruptedly extracts air from a closed container and simultaneously introduces fresh,low-pressure moist air from the external environment,while maintaining specific levels of humidity and/or temperature within the container and upholding a predetermined pressure value.Preservation technology is the collective term for the set of various technical parameters associated with preservation,including pressure,relative humidity,and other relevant factors,to which LP equipment is specifically designed.The theory of LP is characterized by the enhanced diffusion of gases and vapors that enter and exit the commodity in a dynamic manner under low pressure conditions.The theoretical points involve equipment performance,low pressure,the impact of trace concentrations of gases such as O_(2),CO_(2) and C_(2)H_(4) that naturally occur at low pressure,diffusive mass transfer,heat transfer,and impacts on the activity of enzymes associated with maturation and senescence.The technology is characterized by dynamic low pressure,and the range of commodities preserved is comparable to that of refrigeration.However,certain commodities exiting the hypobaric environment possess subsequent preservation advantages that are not available through refrigeration.The main points of the technology encompass an extended sotrage life,a postponement of quality degradation,minimized water loss,the suppression of pathogen growth,and the killing of both internal and external insects of the commodity under dynamic low pressure conditions.The core advantage of LP technology lies in its ability to significantly reduce water loss,inhibit respiration and C_(2)H_(4) action,and pathogen growth,killing insects and modulate the activity of enzymes associated with maturation and senescence in post-harvest fresh horticultural products.Consequently,this technology plays a crucial role in prolonging the post-harvest lifespan of these commodities and mitigating quality degradation.Over the past decade,researchers in China have developed a hypobaric short period treatment technology,grounded in LP theory and technical practice,which is commonly referred to as hypobaric treatment.This method has garnered significant attention,leading to an increase in both domestic and international research.A growing body of literature categorizes LP as hypobaric treatment,while some studies also consider vacuum packaging and modified atmosphere packaging(MAP)as LP or hypobaric treatment.Misunderstandings are exacerbated by confusion surrounding nomenclature,which,in conjunction with pre-existing misconceptions,represents a significant barrier to both the research and practical application of the technology.The successful commercial implementation of a vacuum cold fresh chain,centered on LP or hypobaric treatment technology,may be the sole solution to the prevailing misunderstandings associated with LP.
基金Supported by National Natural Science Foundation of China,No.31001012 and No.31101304Programs for Agricultural Science and Technology Development of Shaanxi Province,China,No.2013K02-16Northwestern Polytechnical University Foundation Science Research Fund,No.JC201278
文摘AIM: To investigate the protective effect of glutamine (Gln) on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment.
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
基金supported by the National Basic Research Development Program of China [2012CB518200]the National Natural Science Foundation of China [31271223 and 31071002]
文摘Chronic intermittent hypobaric hypoxia (CIHH) is a treatment of moderate hypoxia that simulates high altitude interrupted by normoxia. Growing evidence shows that CIHH has multiple beneficial effects on
文摘In recent ten years in China,the application research of hypobaric storage was extended to the non-freeze preservation of cooked food,fresh-cut vegetables,edible fungi and fruits,preliminary processing of growing area and vacuum cold fresh chain to the cold chain breakage for horticultural products,and also to the investigation of principle and theory but the investigation results would have some evident difference. This paper will simply summarize the basic conception,principle,two withdrawing air type hypobaric storage technologies,and introduce many examples as mentioned above extending in China. This paper thinks that the master mechanism of preservation of LP for fresh horticultural products effectively inhibits the activity change of manifold enzymes,which are PAL,POD,PPO,CAT,CAD,SOD et al.,affecting the maturation and caducity of fresh horticultural products during LP storage for a short period,as a result,to reduce both risk of physiology obstacle and disease and to prolong their postharvest life; for the foreseeable future Burg's hypobaric storage technology and hypobaric short period treatment technology will play an important role in the preservation on fresh agricultural products and food preservation in storage and transportation,the preliminary processing of growing area,fresh logistics,establishing the operating platform of perishable food and high business value,fresh e-business,and fresh delivery for scattered families,establishing the operating platform of fresh-cut vegetables including edible fungi and so on in China or in the world.
基金supported by grants from the National Science and Technology Major Project(2014ZX09J14102-05B and 2018ZX09J18109)。
文摘Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.
文摘Effects of hypobaric storage on physiological and biochemical changes in Dong jujube fruit were investigated. Hypobaric storage significantly delayed the decrease in firmness and maintained content of ascorbic acid, reduced accumulation of ethanol and acetaldehyde in pulp and respiration, inhibited activities of ascorbic acid oxidase and alcohol dehydrogenase and slowed down the rate of ethylene production, but had little effect on flesh browning of the fruit.
基金the National Basic Research Program of China(2006CB504100)the National Natural Science Foundation of China (30393131, 30771043)
文摘Objective：To investigate the characteristics of fat metabolism in rat skeletal muscle after hypobaric hypoxia acclimation. Methods： Sprague-Dawley rats were divided into 3 groups randomly： control group （H0）, hypoxic 5-day group （HS）, and hypoxic 15-day group （H15）. Animals of H5 and 15 groups were exposed to hypobaric hypoxia chamber simulating 5 000 m high altitude for 5 d or 15 d respectively, 23 h per day. H0 group stayed outside of chamber The level of fatty acid oxidation and uptake, and glucose oxidation were examined, and the level of non-esterified fatty acids （NEFA）, ATP and phosphocreatine （PCr） were also assayed in rat skeletal muscles. Results： The contents of ATP and PCr in H5 group were lower than those in H0 and H15 groups （P〈0.05）, while there was no significant difference between H0 and H15. Compared with H0, the blood NEFA level in all hypoxia groups was increased significantly （P〈0.05）. The muscle NEFA level in H15 group was greatly higher than that in H0 and H5 groups. The rates of fatty acid oxidation and uptake in H15 group were significantly higher than those in H0 and H5 groups （P〈0.05）, and the rate of glucose oxidation in all hypoxia groups was significantly decreased than that in H0 group （P〈0.05）. Conclusion： It is concluded that the enhanced fat oxidation may be one of the mechanisms in the maintenance of energy homeostasis after hypobaric hypoxic acclimation.
基金This work was supported by grants from Guangxi Medical High-level Key Talents/139/(No.G201901010)Natural Science Foundation of Guangxi Province(No.GXNSFDA198008).
文摘Objective The hypersensitivity of the kidney makes it susceptible to hypoxia injury.The involvement of neutrophil extracellular traps(NETs)in renal injury resulting from hypobaric hypoxia(HH)has not been reported.In this study,we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism.Methods A total of 24 SD male rats were divided into three groups(n=8 each):normal control group,hypoxia group and hypoxia+pyrrolidine dithiocarbamate(PDTC)group.Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters(oxygen partial pressure about 6.9 kPa)for 7 days.PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days.Pathological changes of the rat renal tissues were observed under a light microscope;the levels of serum creatinine(SCr),blood urea nitrogen(BUN),cell-free DNA(cf-DNA)and reactive oxygen species(ROS)were measured;the expression levels of myeloperoxidase(MPO),citrullinated histone H3(cit-H3),B-cell lymphoma 2(Bcl-2),Bax,nuclear factor kappa B(NF-κB)p65 and phospho-NF-κB p65(p-NF-κB p65)in rat renal tissues were detected by qRT-qPCR and Western blotting;the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining.Results After hypoxia,the expression of NF-κB protein in renal tissues was significantly increased,the levels of SCr,BUN,cf-DNA and ROS in serum were significantly increased,the formation of NETs in renal tissues was significantly increased,and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues.When PDTC was used to inhibit NF-κB activation,NETs formation in renal tissue was significantly decreased,the expression level of Bcl-2 in renal tissues was significantly increased,the expression level of Bax was significantly decreased,and renal injury was significantly alleviated.Conclusion HH induces the formation of NETs through the NF-κB signaling pathway,and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.
文摘To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.
文摘Chronic exposure to hypobaric hypoxia (HH) causes memory impairment and prolonged state of mental confusion. However, effect of high altitude exposure on mood state and its underlying mechanisms have been poorly studied.? Present study was undertaken to investigate the mood state alteration following chronic exposure to HH. Male Sprague Dawley rats were divided into five groups and exposed to hypoxia for 3, 7, 14 and 21 days in an animal decompression chamber at an altitude of 25,000ft. Anxiety-and depression-like behaviors were assessed by using various mazes along with changes in serotonin and glutamate level. Our study revealed a decrease in exploratory, grooming and rearing behavior in open field test following initial exposure to HH for 7 days without affecting the locomotory behavior. Initial exposure to HH-decreased time spent in open arm of elevated plus maze indicating induction of anxiety-like behavior which normalized on prolonged hypoxic exposure for 21 days. Hypoxic exposure for 7 days induced anhedonia and increased despair behavior in rat while there was steady improvement in these behaviors when exposed for 21 days. Decrease in serotonin level was noted in hippocampus along with elevated corticosterone and glutamate level which gradually decreased on prolonged exposure to HH. These findings suggest that initial exposure to HH increases transient anxiety-like behavior in rats followed by gradual improvement in mood state on prolonged exposure. Further, the study also indicates the involvement of serotonergic system in mood state alteration at high altitude following chronic exposure and reoxygenation.
文摘The exploration of the effects of pressure leads to new insights into the mycelial growth of Paecilomyces hepiali fungal strain. This strain has been generally accepted as true anamorph of wild Ophiocordyceps sinensis. It is only found at high altitude area like Himalayan plateau where atmospheric pressure is very low. Most of researches about P. hepiali and artificial mycelial cultivation have been done around mean sea level pressure. Then new experimental set up was developed and described. The apparatus permitted growth of mycelia under different pressure levels while other micro environmental conditions were carefully controlled. Potato dextrose broth was used as liquid media. As solid and semi solid media, sorghum base media and potato dextrose agar were prepared. Results of mycelial growth under hypobaric pressures and hyperbaric pressure were compared with mycelial growth of atmospheric pressure and hence growth influence has been shown. Specially, -100 mmHg treated sample showed significantly highest growth in both solid media and semi solid media. In semi solid media, -100 mmHg was not significant with other reduced pressure treatments. Meanwhile, -150 mmHg treated samples showed significantly highest mycelial growth of liquid media and -150 mmHg of pressure adversely affected on water contents of solid growing media. This may be an effect of pressure on enzymatic activities, protein and fatty acid of plasma membrane. As well as, pressure changes equilibrium of biochemical reactions, bond of some molecules and partial pressure of air molecules. Further molecular and biochemical researches are required to evaluate the possible stimulation of mycelial growth through hypobaric and hyperbaric treatments.
文摘Objective:To study the effects of dexmedetomidine combined with hypobaric lumbar anesthesia on pain mediator secretion as well as inflammatory response and stress response activation in elderly patients with hip replacement.Methods: Elderly patients who were>70 years old and underwent hip replacement in Hancheng People's Hospital between March 2015 and June 2017 were chosen and randomly divided into the experimental group who accepted dexmedetomidine combined with hypobaric lumbar anesthesia and the control group who accepted hypobaric lumbar anesthesia alone. The levels of pain mediators and stress mediators in serum as well as the expression of inflammatory molecules in peripheral blood were measured before surgery, the same day after surgery and 3 d after surgery.Results:Compared with those of same group before surgery, CGRP,β-EP, SP, BK, TNF-α, ACTH, F-C, F-Ins, NE and MDA levels in serum as well as NLRP3, Caspase-1, TLR4 and NF-κB mRNA expression in peripheral blood of both groups significantly increased the same day after surgery and 3 d after surgery, and CGRP,β-EP, SP, BK, TNF-α, ACTH, F-C, F-Ins, NE and MDA levels in serum as well as NLRP3, Caspase-1, TLR4 and NF-κB mRNA expression in peripheral blood of experimental group the same day after surgery and 3 d after surgery were significantly lower than those of control group.Conclusion: Dexmedetomidine combined with hypobaric lumbar anesthesia for hip replacement in the elderly can reduce the secretion of pain mediators and relieve the inflammatory response and stress response.
文摘Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.
基金supported by the National Natural Science Foundation of China(81430043,81771239,81974188,and 81901186).
文摘Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness.Autophagy plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains unknown.Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain damage.The autophagic agonist rapamycin only promotes the initiation of autophagy.By proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic flux.Overexpression of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with rapamycin.Furthermore,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure.These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
基金supported by the National Natural Science Foundation of China(31071002,31271223,31671184,and 81800308)the National Basic Research Development Program of China(2012CB518200)the Natural Science Foundation of Hebei Province(C2012206001),China
文摘Chronic intermittent hypobaric hypoxia(CIHH)is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension(RVH). In this study, RVH was induced by the 2-kidney-1-clip method(2 K1 C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure(ABP), heart rate(HR), and renal sympathetic nerve activity(RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii(NTS) in anesthetized rats.Evoked excitatory postsynaptic currents(eEPSCs) and spontaneous EPSCs(sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase(nNOS) and endothelial NOS(eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHHtreated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and e NOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via upregulating NOS expression in the NTS.
基金supported by the National Natural Science Foundation of China(81790632,31970863,and 31970088)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2020YFA0509600)。
文摘The gut microbiota is involved in host responses to high altitude.However,the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood.Here,we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome,short-chain fatty acids(SCFAs),and bile acids(BAs)over 28 d.We identified weight loss,polycythemia,and pathological cardiac hypertrophy in hypoxic rats,accompanied by a large compositional shift in the gut microbiota,which is mainly driven by the bacterial families of Prevotellaceae,Porphyromonadaceae,and Streptococcaceae.The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides,Alistipes,and Lactococcus genera and a larger Bacteroides to Prevotella ratio.Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces,suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge.Interestingly,the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota,partially inhibited the increased abundance of the Bacteroides and Alistipes genera,restored the decrease of plasma propionate,and moderately ameliorated cardiac hypertrophy in hypoxic rats.Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge.Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.
基金supported by the National Natural Science Foundation of China (81770402)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010201)National Key R&D Program of China (2017YFA 0103700, 2016YFC1301204)
文摘Dear Editor,Myocardial injury following ischemia/reperfusion(I/R)is a common clinical scenario in patients suffering from ischemic heart disease(Hausenloy et al.,2016).The involvement of proteins and signaling pathways is well studied in myocardial I/R injury and protection(Hausenloy et al.,2016;Yang et al.,2012),however,more than 98%of the transcriptional output in mammals are noncoding RNAs(ncRNAs).These products range from short microRNAs(miRNAs)to long noncoding RNAs(lncRNAs,Das et al.,2018)and modulate critical pathophysiologic mechanisms,such as apoptosis,oxidative stress,Ca2+overload and inflammation,during myocardial I/R injury and protection(Das et al.,2018).
基金This work was supported by grants from the National Natural Science Foundation of China(No.61527807)the Key Program of the National Natural Science Foundation of China(No.81630003).
文摘Background:Hypobaric hypoxia(HH)exposure at high altitudes can result in a decline in cognitive function,which may have a serious impact on the daily life of people who migrate to high altitudes.However,the specific HH-induced changes in brain function remain unclear.This study explored changes in brain activity in rats exposed to a sustained HH environment using functional magnetic resonance imaging(fMRI).Methods:Healthy male rats(8 weeks old)were randomly divided into a model group and a control group.A rat model of cognitive impairment induced by sustainedHHexposure was established.The control and model groups completed training and testing in the Morris water maze(MWM).A two-sample t-test for between-group difference comparisons was performed.Repeated measures analyses of variance for within-group comparisons were performed and post-hoc comparisons were made using the Tukey test.Between-group differences in spontaneous brain activity were assessed using a voxel-wise analysis of resting-state fMRI(rs-fMRI),combined with analyses of the fractional amplitude of low frequency fluctuations(fALFF)in statistical parametric mapping.Results:In the MWM test,the escape latencies of the model group were significantly longer compared with those of the control group(control group vs.model group,day 1:21.6±3.3 s vs.40.5±3.4 s,t=–11.282;day 2:13.5±2.2 s vs.28.7±5.3 s,t=–7.492;day 3:10.5±2.8 s vs.22.6±6.1 s,t=–5.099;day 4:9.7±2.5 s vs.18.6±5.2 s,t=–4.363;day 5:8.8±2.7 s vs.16.7±5.0 s,t=–3.932;all P<0.001).Within both groups,the escape latency at day 5 was significantly shorter than those at other time points(control group:F=57.317,P<0.001;model group:F=50.718,P<0.001).There was no within-group difference in average swimming speed(control group,F=1.162,P=0.956;model group,F=0.091,P=0.880).Within the model group,the time spent within the original platform quadrant was significantly shorter(control group vs.model group:36.1±5.7 s vs.17.8±4.3 s,t=7.249,P<0.001)and the frequency of crossing the original platform quadrant was significantly reduced(control group vs.model group:6.4±1.9 s vs.2.0±0.8 s,t=6.037,P<0.001)compared with the control group.In the rs-fMRI study,compared with the control group,rats in the model group showed widespread reductions in fALFF values throughout the brain.Conclusions:The abnormalities in spontaneous brain activity indicated by the fALFF measurements may reflect changes in brain function after HH exposure.This widespread abnormal brain activity may help to explain and to provide new insights into the mechanism underlying the impairment of brain function under sustained exposure to high altitudes.
基金Natural Science Foundation of Lanzhou Military Area Command(No.CLZ13JA01)
文摘Objective To observe pancreatic ER kinase （PERK） signaling of unfolded protein response （UPR）. Methods The rats were divided into control, model, and ginsenoside Rb; （Rbl） groups, and put into hypoxia chamber to establish the acute plateau stress model. The water solutions of Rbl were given to rats in Rb; group for 7 d. After that, The behavior of rats was observed by Y-maze and passive avoidance test and the rats were sacrificed in a batch for detection by Western blotting. Results Hypobaric hypoxia mediated UPR pathway accompanied the activation of protective pathways such as PERK-elF2a-ATF4 and Grp78/Bip pathways. On the other hand, RbT, the extract from herbal medicine ginseng, increased on the expression of PERK, eIF2a, ATF4, and Grp78/Bip in rats. Conclusion The results indicate that PERK-elF2a-ATF4-GRP78 pathway is a potential target for therapeutic applications in high altitude diseases and Rb] can attenuate the injury to memory function caused by hypobaric hypoxia neurotoxicity.
