大鼠小肠缺血预适应对缺血-再灌注损伤保护作用及机制

目的:探讨小肠缺血预适应(ischemic preconditioning,IP)对缺血再灌注(ischemia／reperfusion,I／R)肠黏膜损伤的保护作用及可能机制。方法:以大鼠肠系膜前动脉制造I／R和IP模型;用分光光度法测血和肠组织二胺氧化酶(diamine oxidase,DAO)活性;用H-E和PAS特染显示肠黏膜的病理改变并进行Chiu CJ评分;用免疫组化方法显示肠绒毛CGRP、NPY肽能神经并用测微尺测定阳性神经纤维密度。结果:与对照组相比,I／R组及IP I／R组血DAO水平升高而肠黏膜DAO水平降低,肠黏膜损伤Chiu CJ评分数升高;肠绒毛CGRP阳性神经纤维密度降低而NPY阳性神经纤维密度升高;但IP轻于I／R的变化。结论:小肠IP能减轻I／R引起的肠黏膜机械屏障的组织病理损伤,其机制是通过肠黏膜局部CGRP、NPY肽能神经参与调节其微血管舒缩平衡而实现的。

Protective effects of small intestinal ischemic preconditioning on ischemia/reperfusion injury and its mechanism

Objective: To investigate the protective effect of ischemic preconditioning on gut barrier function injury induced by ischemia/reperfusion (I/R) in rat small intestine and to study the mechanism. Methods: The intestinal I/R injury and IP protective experimental models were induced by occluding the superior mesenteric artery (SMA) 30 min via an atraumatic arterial clamp, following 60 min of reperfusion, and by 3 cycles of 8 min SMA occlusion and 10 min reperfusion before prolonged I/R. The diamine oxidase (DAO) activity in intestinal tissue and blood were determined by spectrophotometry. The pathological change of intestinal mucosa was evaluated by Chiu J examing standard before stainned by H. E and PAS. The changes of the intersection-point density of CGRP-IR and NPY-IR positive nerve fibers in intestine were measured by " " micrometer-ruler after the villi had been dyed by the immunohistochemical methods. Results: Compared with control group, higher level of blood DAO activity, lower level of intestinal DAO activity, and higher grade of intestinal mucosal damage were observed by Chiu J examing standard; higher density of CGRP-IR positive nerve fiber and lower density of NPY-IR positive nerve fiber were found in I/R group. IP prevented all the above changes induced by I/R. Conclusion: Ischemic preconditioning has protective effects on gut barrier function injury induced by ischemia/reperfusion, which may be through regulating the dilation and constraction banlance of intestinal mucosal microvessel by CGRP-IR and NPY-IR positive nerve fiber in intestinal mucosa.