蛋白激酶C活性对缺血再灌注心肌环氧化酶表达的影响

Effect of PKC activity on the expression of COX-2 in rats with myocardial ischemia-reperfusion injury

目的探讨心肌缺血再灌注过程中蛋白激酶C(PKC)活性变化对缺血再灌注损伤心肌的影响及机制。方法将40只大鼠随机分为模型组、观察1组、观察2组及对照组各10只,前三组均采用冠状动脉分支结扎术制备心肌缺血再灌注模型,再灌注1 h后结束实验;其中观察1组和观察2组分别于冠状动脉结扎术前20 min经股静脉注射佛波酯及多黏菌素B;对照组为假手术组。实验结束后各组均取静脉血,采用化学比色法测定肌酸激酶(CK)和丙二醛(MDA)水平;处死动物,取心肌组织,采用免疫组化法检测PKC和环氧化酶-2(COX-2)表达。结果与对照组比较,模型组血清CK、MDA水平明显升高(P<0.01),心肌PKC表达无明显差异、COX-2表达明显升高(P<0.05);与观察2组相比,观察1组血清CK、MDA水平明显降低(P<0.05),心肌PKC表达明显升高、COX-2表达明显降低(P均<0.01)。结论 PKC激活有利于减轻心肌氧化应激损伤,可能机制为下调COX-2表达;此为心肌缺血再灌注损伤的防治提供了依据。

Objective To investigate the effect and mechanism of protein kinase C（PKC） on myocardial ischemia reperfusion.Methods Forty rats were randomly divided into model group,observation group 1,observation group 2 and control group with 10 in each.Model of myocardial ischemia by coronary artery ligation was prepared in the first three groups,and then followed by reperfusing for 1 hour.Observation group 1 and 2 were injected with phorbol ester and polymyxin B through femoral vein about 20 min before coronary artery ligation.The control group was sham-operated group.Venous blood was collected after the experiment,the concentration of creatine kinase（CK） and malondialdehyde（MDA） were detected by chemical colorimetry;myocardium was obtained after the rats were executed,then the expression of PKC and cyclooxygenase-2（COX-2） were detected by immunohistochemistry.Results Compared with the control group,concentration of serum CK,MDA in model group were significantly higher（P〈0.01）,PKC expression was not significantly different,but the COX-2 expression was significantly higher（P〈0.01）;compared with observation group 2,concentration of serum CK,MDA concentration in observation group 1 decreased significantly（P〈0.05）,PKC expression was significantly higher,COX-2 expression was significantly lower（both P〈0.01）.Conclusions PKC activation is conducive to reduce myocardial oxidative stress,the possible mechanism is to decrease the expression of COX-2;this study can provide basis for the myocardial ischemia reperfusion.