促红细胞生成素对心肌缺血再灌注后诱导型一氧化氮合酶蛋白的影响

目的:探讨促红细胞生成素对大鼠心肌缺血再灌注后诱导型一氧化氮合酶蛋白的影响及其对心肌保护作用与机制。方法:采用结扎左冠状动脉前降支30min,再灌注120min的方法,建立大鼠模型缺血再灌注损伤模型,将30只大鼠随机分为对照组、缺血再灌注组、治疗组(EPO 5000IU/kg)3组,每组10只,测定再灌注末血清和心肌组织磷酸肌酸激酶(CK)、丙二醛(MDA)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)的变化,应用免疫组织化学方法检测iNOS蛋白的表达,用TUNEL法检测心肌细胞凋亡的变化。结果:与正常对照组相比,缺血再灌注组细胞上清液中LDH、MDA含量明显升高(P<0.01),SOD活力则显著降低(P<0.01),缺血组再灌注组凋亡率均升高明显(P<0.01)。治疗组的LDH、MDA显著低于对照组和缺血再灌注组(P<0.01),SOD则高于对照组和缺血再灌注组(P<0.01),缺血再灌注后细胞凋亡率与对照组相比均明显升高(P<0.01),治疗组再灌组的凋亡率与对照组相比均显著下降(P<0.01)。对照组有少量iNOS表达,缺血再灌注组iNOS表达升高(P<0.01)而EPO治疗组表达减少(P<0.01),与缺血再灌注组相比差异有显著性意义(P<0.01)。结论:EPO抑制iNOS蛋白的表达以减少心肌细胞凋亡,减轻大鼠心肌缺血再灌注损伤,从而对心肌有保护作用。

The Effect of Erythropoietin on iNOS Expression after Myocardial Ischemia reperfusion Injury in Rats

Objective:To explore the effect of erythropoietin(EPO) on iNOS(induced nitricoxide synthase) expression after myocardial ischemia reperfusion injury in rats.Method: The left anterior descending coronary artery was ligated for 30 minutes and then loosed for120 minutes to establish the rat model of myocardial ischemic-reperfusion injury.Thirty Wistar rats were randomly divided into three groups: sham-operation,ischemic-reperfusion,EPO treatment(5000IU/kg).The levels of serum MDA(malondialdehyde),SOD(superoxide dismutase),CK(creatinine kinase),LDH(lactate dehydrogenase) were detected at reperfusion for 120min.The expression of iNOS was examined by immunocytochemical stamping and the cardiomyocyte apoptosis was examined by TUNEL techniques.Result: Compared with the control group of ischemic reperfusion,EPO significantly reduced serum CK,myocardial MDA,LDH content and the activity of myocardial SOD.The expression of iNOS was increased during ischemic reperfusion injury.In EPO-treated group,the expression of iNOS was down-regulated,and iNOS were reduced.compared with the ischemic group,the number of TUNEL-positive cells in the EPO group was significantly decreased.Conclusion: These results indicated that EPO down-regulating the expression of iNOS and decreased the myocardial ischemic reperfusion injury.