RhoA-MMP-2信号通路在缺血预处理保护糖尿病大鼠心肌缺血再灌注中的作用  

Protective effects of ischemia preconditioning on myocardial ischemia reperfusion injury of diabetic rats:the role of RhoA-MMP-2 signal pathway

作　　者：贾俊海[1] 周留正[1] 陈素仙[1] 潘伟[1] 贾鹏[1] 

机构地区：[1]江苏大学基础医学与医学技术学院,江苏镇江212013

出　　处：《中国现代医学杂志》2011年第18期2106-2110,共5页China Journal of Modern Medicine

基　　金：江苏大学高级人才基金(No:09JDG036)

摘　　要：目的探讨糖尿病心肌缺血再灌注损伤的发生机理,观察RhoA-MMP-2信号转导通路在缺血预处理保护糖尿病大鼠心肌缺血再灌注中的作用。方法 SD大鼠40只,分为非糖尿病心肌缺血再灌注(CIR)组、非糖尿病心肌缺血预处理(CIP)组、糖尿病心肌缺血再灌注(DIR)组和糖尿病心肌缺血预处理(DIP)组。免疫组织化学法检测心肌MMP-2蛋白的表达,Western blot法测定心肌RhoA和ROCK蛋白的表达,检测血清和心肌组织中NO、NOS、SOD和MDA的水平,进行心肌梗死范围的测定。结果与DIR组相比,DIP组血清和心肌中的MDA含量明显降低,血清和心肌中的SOD活性明显升高。与DIR组相比,DIP组血清和心肌中的NO含量明显降低,血清和心肌中的NOS活性明显降低。与DIR组相比,DIP组心肌中的MMP-2蛋白表达明显降低。CIP组的心肌梗死面积较CIR组降低;DIP组的心肌梗死面积较DIR组降低;与CIP组比较,DIP组的心肌梗死面积显著增加。DIP组中RhoA蛋白的表达明显低于DIR组。DIP组中ROCK蛋白的表达明显低于DIR组。结论缺血预处理可减轻糖尿病大鼠的心肌缺血再灌注损伤,可能与减轻脂质过氧化和自由基损伤、下调MMP-2、RhoA和ROCK蛋白的表达以及降低心肌梗死的范围等有关。[ Objective ] The purpose of this study was to explore the pathophysiological mechanisms underlying isehemia reperfusion injury in diabetic rat heart. To investigate the protective effects of ischemia preconditioning （IPC） on myocardial ischemia reperfusion injury in diabetic rats. [Methods] Following 4 weeks of strcptozotoeininduced diabetic rats, all hearts were divided randomly into four groups： non-diabetic ischemia reperfusion group （CIR group）, non-diabetic ischemia preconditioning group （CIP group）, diabetic IR group （DIR group）, diabetic ischemia preconditioning group （DIP group）. In IR group, the injury was induced by occlusion of the left anterior descending coronary after 30 rain followed by reperfusion 120 min. In IP group, preconditioning consisted of three cycles of 5 rain ischemia and 5 min reperfusion, prior to ischemia. At the end of the experiment, checked infarct size. The protein expressions of MMP-2 were evaluated by immunohistochemieal method. The RhoA and ROCK protein expressions were assessed by western blot assay. The contents of MDA and NO in serum and myocardium were detected. The activities of SOD and NOS in serum and myoeardium were measured. [ Results ] Compared with that of DIR group, the levels of MDA in serum and myoeardium were decreased significantly, the activities of SOD inserum and myocardium were increased significantly in DIP group. Compared with that of DIR groups. The expression of MMP-2 and RhoA and ROCK in DIP group were decreased. Compared with that of DIR group, the contents of NO in serum and myocardium were decreased significantly; the activities of NOS in serum and myocardium were decreased significantly in DIP group. And the myocardial infarct sizes were reduced significantly. [Conclusions] IPC could reduce the severity of reperfusion induced myocardial infarct size, protects myocardial structure in nondiabetic rats. In 4 weeks diabetes afford the same myocardium protection as in non-diabetic rats. /PC has obvious cardiopmtective effects on m

关 键 词：糖尿病 缺血再灌注损伤 缺血预处理 RHOA 基质金属蛋白酶-2 自由基 

分 类 号：R363[医药卫生—病理学]