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乌司他丁通过抑制肠黏膜细胞凋亡减轻大鼠肠道缺血-再灌注损伤
The protective effect of ulinastatin on the intestinal mucosal barrier in rats after intestinal ischemia-reperfusion
【摘要】 目的探讨蛋白酶抑制剂乌司他丁(ulinastatin,UTI)对大鼠肠缺血-再灌注损伤后肠黏膜屏障功能的保护作用及其机制。方法 24只成年雄性SD大鼠夹闭肠系膜上动脉1 h,再灌注1 h,随机分为空白对照组、对照组和治疗组。治疗组于缺血后经阴茎背静脉缓慢泵入UTI(5万单位/kg);对照组给予等量等渗盐水;空白对照组仅做开关腹并给予等量生理盐水作为对照。各组大鼠均于制模后采集标本,动态浊度法检测血清内毒素含量,TUNEL法检测肠黏膜上皮细胞凋亡率,RT-PCR检测凋亡调控基因Bax、Bcl-2 mRNA的表达。结果空白对照组血清内毒素水平和肠黏膜细胞凋亡指数均低于对照组(P<0.01);治疗组Bax mRNA表达低于对照组(P<0.01),而Bcl-2 mRNA表达高于对照组(P<0.01)。结论乌司他丁可能通过抑制肠黏膜上皮细胞的凋亡,维持肠黏膜屏障的完整性,从而防止缺血-再灌注损伤时细菌和内毒素的移居。
【Abstract】 Objective To investigate the protective effect of ulinastatin on the intestinal mucosal barrier in rats with ischemia-reperfusion.Methods Totally 24 SD rats were randomly divided into 3 groups after clamping superiormesenteric artery for 1 h and reperfusion for 1 h: blank control group,control group and treatment group.Rats in the treatment group were injected with ulinastatin(50 000 U/kg) through vena dorsalis penis after ischemia-reperfusion model was induced.The control group underwent laparotomy with only the manipulation of the intestine and the same dose of saline was used through the same way.Specimens were obtained after ischemia-reperfusion model was induced.Dynamic turbidimetry was used to evaluate the effect of ulinastatin on the intestinal endotoxin translocation in rats.Apoptosis of mucosal cells was detected by TUNEL method,and the expressions of Bax and Bcl-2 mRNA were determined by semi-quantitative RT-PCR.Results The serum endotoxin level and apoptotic index of mucosal cells were evidently lower in blank control group than in control group(P<0.01).The expression of Bax mRNA in intestinal mucosal cells was lower in treatment group than in control group(P<0.01),but the expression of Bcl-2 mRNA was lower in treatment group(P<0.01).Conclusion Ulinastatin can prevent the translocation of bacteria and endotoxin in ischemia-reperfusion injury by inhibiting the apoptosis of intestinal mucosa cells and maintaining the intestinal barrier function.
【Key words】 ulinastatin; ischemia-reperfusion; cell apoptosis; Bax; Bcl-2;
- 【文献出处】 西安交通大学学报(医学版) ,Journal of Xi’an Jiaotong University(Medical Sciences) , 编辑部邮箱 ,2010年05期
- 【分类号】R965
- 【被引频次】23
- 【下载频次】136