乌司他丁在肠道缺血再灌注损伤中抗炎作用的新靶点——自身消化假说  

A New Target of Ulinastatin for Anti-inflammatory Action During Superior Mesenteric Artery Occlusion and Reperfusion: The Self-digestion Hypothesis

作　　者：韦祎[1] 陈仲清[1] 郭培培[1] 曾振华[1] 陈辉[1] 傅卫军[1] 

机构地区：[1]南方医科大学南方医院重症医学科,广州510515

出　　处：《数理医药学杂志》2013年第2期138-142,共5页Journal of Mathematical Medicine

基　　金：天普研究基金(01201028)

摘　　要：目的:验证自身消化假说及探讨乌司他丁抗炎作用的机制以及肠道胰蛋白酶在休克以及炎症反应中的作用。方法:雄性WISTAR大鼠,腹腔麻醉后在十二指肠近端及回肠末端置入软管用于肠道灌洗,通过阻断肠系膜上动脉血流复制肠道缺血再灌注模型,将实验动物随机分为对照组(sham group)、肠道缺血再灌注但不灌洗肠道组(SMAO group)、肠道缺血再灌注且用生理盐水灌洗肠道组(SMAO+NS group)、肠道缺血再灌注且用乌司他丁灌洗肠道组(SMAO+UTI group)。对比各组大鼠的动脉血压,生存时间,肠液胰蛋白酶活性,肠道粘膜病理变化,白细胞表面粘附分子CD11b,以及血浆中肿瘤坏死因子-α(TNF-α)和白介素1(IL-1)水平。结果:随着肠道胰蛋白酶活性的降低,乌司他丁灌洗组大鼠血中TNF-α、IL-1及PMN CD11b水平明显低于盐水灌洗组(P<0.05),且血流动力学明显优于盐水灌洗组,生存时间明显延长。结论:乌司他丁可以通过抑制肠道胰蛋白酶活性发挥抗炎作用,胰酶对肠壁组织的自身消化作用可能是全身炎症反应综合征(SIRS)以及多器官功能障碍综合征(MODS)的启动机制。Objective： To test the self-digestion hypothesis and investigate the anti-inflammation mechanism of UTI（ulinastatin）.Methods： Male Wistar rats were randomized into A group（A）,superior mesenteric artery occlusion and reperfusion（I/R） group（B）,lumen perfusion with NS in I/R group（C） and lumen perfusion with UTI in I/R group（D）.The lumen of the proximal duodenum and the terminal ileum were cannulated for intestinal perfusion.Intestinal ischemia was produced by occlusion of the superior mesenteric arteries.The mean arterial blood pressure（MAP）,survival time,protease activity of the intestinal fluid,levels of TNF-α、IL-1 and PMN CD11b and the pathology of the intestinal mucosa was observed comparatively.Results： With the blockage of the pancreatic enzymes by UTI in the intestine,there is significantly lower levels of TNF-α、IL-1 and PMN CD11b,the femoral artery blood pressure is maintained close to control levels.Conclusion： Intestinal perfusion of ulinastatin can attenuate inflammation by the blockage of pancreatic enzymes.These results indicate the hypothesis that pancreatic digestive enzymes in the ischemic intestine may be a trigger mechanism of SIRS and MODS.

关 键 词：肠道缺血再灌注损伤 休克 炎症 肠道胰蛋白酶 乌司他丁 自身消化 

分 类 号：R657.3[医药卫生—外科学]