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NRIP1通过转录激活HMGB1参与脓毒症引起的肠道上皮细胞损伤的作用研究
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作者 崔文娟 刘芹 +1 位作者 樊晓光 乔鲁军 《中国免疫学杂志》 北大核心 2025年第2期328-335,共8页
目的:探究核受体相互作用蛋白1(NRIP1)通过转录调控高迁移率族蛋白B1(HMGB1)对脓毒症引发的肠道上皮细胞损伤的作用。方法:RT-qPCR和Western blot检测NRIP1和HMGB1表达水平。HE染色检测大鼠肠道组织的病理学变化;CCK-8法确定LPS的最佳... 目的:探究核受体相互作用蛋白1(NRIP1)通过转录调控高迁移率族蛋白B1(HMGB1)对脓毒症引发的肠道上皮细胞损伤的作用。方法:RT-qPCR和Western blot检测NRIP1和HMGB1表达水平。HE染色检测大鼠肠道组织的病理学变化;CCK-8法确定LPS的最佳处理时间。利用NRIP1小干扰RNA(siRNA-NRIP1-1/2)转染Caco-2细胞,采用CCK-8法和流式细胞术分别检测细胞活力和凋亡;RT-qPCR和Western blot分析炎症相关因子表达;跨上皮电阻(TEER)检测肠道上皮通透性;Western blot检测凋亡和紧密连接相关的蛋白表达。荧光素酶报告实验和染色质免疫沉淀法(ChIP)验证NRIP1与HMGB1的结合关系。在LPS处理的Caco-2细胞中同时敲低NRIP1并过表达HMGB1后再次进行功能实验。结果:NRIP1在脓毒症大鼠肠道组织和LPS诱导的Caco-2细胞中表达增加。干扰NRIP1后抑制LPS诱导的Caco-2细胞活性损伤、凋亡、炎症反应和屏障损伤。此外,NRIP1可转录激活HMGB1表达,过表达HMGB1可逆转NRIP1缺失对Caco-2细胞活力、凋亡、炎症反应以及屏障功能的影响。结论:NRIP1可促进脓毒症引发的肠道上皮细胞损伤,其机制可能与HMGB1的转录激活相关。 展开更多
关键词 NRIP1 HMGB1 脓毒症 肠道上皮细胞损伤
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Protective effects of Rheum tanguticum polysaccharide against hydrogen peroxide-induced intestinal epithelial cell injury 被引量:11
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作者 Lin-NaLiu Qi-BingMei LiLiu FengZhang Zhen-GuoLiu Zhi-PengWang Ru-TaoWang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第10期1503-1507,共5页
AIM: To describe the effect of Rheum tanguticum polysaccharide (RTP) on hydrogen peroxide-induced human intestinal epithelial cell injury. METHODS: Hydrogen peroxide (100 μmol/L) was introduced to induce human intest... AIM: To describe the effect of Rheum tanguticum polysaccharide (RTP) on hydrogen peroxide-induced human intestinal epithelial cell injury. METHODS: Hydrogen peroxide (100 μmol/L) was introduced to induce human intestinal epithelial cell injury. Cells were pretreated with RTP (30,100,300 μg/mL) for 24 h before exposure to hydrogen peroxide. Cell viability was detected by MTT assay and morphological observation. Acridine orange staining and flow cytometry were performed to assess cell apoptosis. Lactate dehydrogenase (LDH) activity, production of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by spectrophotometry with corresponding assay kits. RESULTS: Following exposure to H2O2, a marked decrease in cell survival and SOD activity, increased production of MDA, LDH leakage and cell apoptosis were found. Pretreatment of the cells with RTP could significantly elevate cell survival, SOD activity and decrease the level of MDA, LDH activity and cell apoptosis. CONCLUSION: RTP may have cytoprotective and anti-oxidant effects against H2O2-induced intestinal epithelial cell injury by inhibiting cell apoptosis and necrosis. This might be one of the possible mechanisms of RTP for the treatment of ulcerative colitis in rats. 展开更多
关键词 Rheum tanguticum polysaccharide Intestinal epithelial cells APOPTOSIS NECROSIS CATALASE
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Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin 被引量:3
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作者 Mohamed A Fahim Hazem Kataya +3 位作者 Rkia El-Kharrag Dena AM Amer Basel al-Ramadi Sherif M Karam 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第33期3836-3841,共6页
AIM:To examine the influence of ghrelin on the regenerative potential of gastrointestinal(GI)epithelium.METHODS:Damage to GI epithelium was induced in mice by two intravenous injections of doxorubicin(10 and 6 mg/kg).... AIM:To examine the influence of ghrelin on the regenerative potential of gastrointestinal(GI)epithelium.METHODS:Damage to GI epithelium was induced in mice by two intravenous injections of doxorubicin(10 and 6 mg/kg).Some of the doxorubicin-treated mice received a continuous subcutaneous infusion of ghrelin(1.25μg/h)for 10 d via implanted mini-osmotic pumps.To label dividing stem cells in the S-phase of the cell cycle,all mice received a single intraperitoneal injection of 5'-bromo-2'-deoxyuridine(BrdU)one hour before sacrifice.The stomach along with the duodenum were then removed and processed for histological examination and immunohistochemistry using anti-BrdU antibody.RESULTS:The results showed dramatic damage to the GI epithelium 3 d after administration of chemotherapy which began to recover by day 10.In ghrelintreated mice,attenuation of GI mucosal damage was evident in the tissues examined postchemotherapy.Immunohistochemical analysis showed an increase in the number of BrdUlabeled cells and an alteration in their distribution along the epithelial lining in response to damage by doxorubicin.In mice treated with both doxorubicin and ghrelin,the number of BrdUlabeled cells was reduced when compared with mice treated with doxorubicin alone.CONCLUSION:The present study suggests that ghrelin enhances the regenerative potential of the GI epithelium in doxorubicintreated mice,at least in part,by modulating cell proliferation. 展开更多
关键词 Gastrointestinal cell proliferation Gastrointestinal mucosal damage GHRELIN
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Hemolysis results in impaired intestinal microcirculation and intestinal epithelial cell injury
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作者 Sebastiaan J Hanssen Tim Lubbers +3 位作者 Caroline M Hodin Frits W Prinzen Wim A Buurman Michael J Jacobs 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第2期213-218,共6页
AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Spragu... AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Sprague-Dawley rats received water or FHb infusion.Microcirculatory changes in jejunum,ileum and colon were evaluated using fluorescent microspheres.Intestinal injury was quantified as plasmatic release of ileal lipid binding protein(iLBP) and verified by histological analysis of the ileum. RESULTS:Water and FHb infusions resulted,when compared with saline infusion,in reduced intestinal microcirculation(after 30 min P<0.05,or better;after 60 min FHb infusion P<0.05 for jejunum and colon) .Circulating FHb levels correlated significantly with release of iLBP(Spearman r=0.72,P=0.0011) .Epithelial cell injury of the villi was histologically observed after water and FHb infusions. CONCLUSION:This study shows that circulating FHb leads to a reduction in intestinal microcirculatory blood flow with marked injury to intestinal epithelial cells. These data support the hypothesis that circulating FHb contributes to the development of intestinal injury. 展开更多
关键词 HEMOGLOBIN MICROCIRCULATION Organ injury VASOCONSTRICTION
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