摘要
为了探究暴露低压低氧不同时间以及移植高原鼠兔、高原鼢鼠肠道菌群后暴露低压低氧环境是否会影响SD大鼠海马组织β淀粉样蛋白(beta-amyloid protein, Aβ)、tau及脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)的表达水平,首先将SD大鼠随机分为常氧组、低压低氧组和低压低氧处理组,低压低氧组根据暴露低压低氧时间又分为第1、3、7、15、28天组,低压低氧处理组则根据处理因素分为低压低氧对照组、低压低氧+抗生素处理组、低压低氧+抗生素+鼢鼠菌处理组、低压低氧+抗生素+鼠兔菌处理组、低压低氧+抗生素+SD大鼠菌处理组(10只/组),共11组;然后采用尼氏染色观察常氧组和低压低氧组海马组织神经细胞的形态变化,采用Western-blot检测各组Aβ、tau及BDNF蛋白表达水平。结果显示,与常氧组相比,低压低氧组从第3天开始海马组织CA1区的神经细胞排列疏松紊乱,细胞核固缩明显,并具有时间依赖性;Aβ、tau蛋白水平分别从低压低氧暴露第7天、3天开始显著升高,并随低压低氧暴露时间的延长进一步升高,其中以tau蛋白升高尤为明显;BDNF蛋白在低压低氧暴露初期显著升高,而后随低压低氧暴露时间的延长逐渐降低,与Aβ和tau蛋白水平呈现显著的负相关。此外,与抗生素处理组相比,在低压低氧环境下,移植高原鼠兔肠道菌群的大鼠海马组织中Aβ、tau蛋白的表达显著下降, BDNF的表达明显升高。实验结果初步表明,低压低氧可上调大鼠海马组织Aβ、tau蛋白表达,下调BDNF蛋白表达;肠道菌群移植可上调低压低氧环境下大鼠海马组织BDNF蛋白的表达,同时影响Aβ、tau蛋白的表达,其中高原鼠兔肠道菌群移植大鼠海马组织中的Aβ、tau蛋白水平被下调,高原鼢鼠肠道菌群移植大鼠海马组织中的tau蛋白水平被上调, Aβ蛋白水平被下调。
In order to explore whether hypobaric hypoxia exposure time and transplantation of plateau pika and plateau zokor intestinal flora will affect the expression of beta-amyloid protein(Aβ),tau and brain-derived neurotrophic factor(BDNF)in hippocampus of the Sprague-Dawley(SD)rats,SD rats were first randomly divided into normoxia group,hypobaric hypoxia group and hypobaric hypoxia treatment group.The rats in the hypobaric hypoxia group were further divided according to the exposure time(1,3,7,15,and 28 days)to hypobaric hypoxia,while those in the hypobaric hypoxia treatment group were further divided according to the treatment factors:hypobaric hypoxia(as a control),hypobaric hypoxia+antibiotic treatment,hypobaric hypoxia+antibiotic+zokor fungus treatment,hypobaric hypoxia+antibiotic+pika fungus treatment,hypobaric hypoxia+antibiotic+SD rat fungus treatment.Therefore,there were totally 11 groups,each having 10 rats.The morphological changes of hippocampal neurons in normoxia group and hypobaric hypoxia group were observed by Nissl staining.The expression levels of Aβ,tau and BDNF proteins in each group were detected by Western-blot.The results showed that,compared with the normoxia group,the hypobaric hypoxia group had loosely arranged and disordered neurons in the hippocampal CA1 area from the third day,with obvious nuclear condensation appearing in a time-dependent manner.The levels of Aβand tau proteins were significantly increased from the 7th and 3rd days,respectively,of hypobaric hypoxia exposure,and further in-creased with the time of exposure,especially the level of tau protein.The BDNF protein level increased significantly in the early stage of hypobaric hypoxia exposure,and then decreased gradually with the exposure time,showing a significantly negative correlation with the Aβand tau protein levels.In addition,compared with rats in antibiotic treatment group,rats transplanted with intestinal flora of plateau pika had significantly decreased expression of Aβ and tau proteins and significantly increased expression of BDNF in the hippocampus under hypobaric hypoxia.The results revealed that hypobaric hypoxia could up-regulate the expres-sion of Aβ and tau proteins and down-regulate the expression of BDNF protein in hippocampus of rats,and that intestinal flora transplantation could up-regulate the expression of BDNF protein in hippocampus of rats in a hypobaric hypoxic environment and also affect the expression of Aβ and tau protein.Transplantation with plateau pika intestinal flora down-regulated the levels of Aβ and tau proteins,while transplantation with plateau zokor intestinal flora up-regulated the level of tau protein and down-regulated the Aβ protein.
作者
黄灵泉
李清月
冯江鹏
陈征
姜欣宇
王书祥
靳国恩
HUANG Lingquan;LI Qingyue;FENG Jiangpeng;CHEN Zheng;JIANG Xinyu;WANG Shuxiang;JIN Guoen(Department of Basic Medicine,Medical College,Qinghai University,Xining 810016,Qinghai,China;College of Agriculture and Animal Husbandry,Qinghai University,Xining 810016,Qinghai,China;Department of Clinical Medicine,Medical College,Qinghai University,Xining 810016,Qinghai,China;Research Center for High Altitude Medicine,Medical College,Qinghai University,Xining 810016,Qinghai,China;Key Laboratory of Plateau Medicine of Ministry of Education,Xining 810016,Qinghai,China;Key Laboratory of Basic Application of Plateau Medicine in Qinghai Province,Xining 810016,Qinghai,China)
出处
《生命科学研究》
CAS
2024年第2期113-120,共8页
Life Science Research
基金
国家自然科学基金资助项目(81974283)
国家重点研发计划项目(2022YFC2403705)。
