二氮嗪预处理对心肌缺血再灌注损伤的保护作用及对连接蛋白43的影响
The protective effect of diazoxide preconditioning on myocardial ischemia-reperfusion injury and the influence on connexin 43
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摘要: 目的:观察二氮嗪预处理(DPC)对大鼠在体心肌缺血再灌注损伤(MIRI)的保护作用及对心室肌连接蛋白43(connexin43,Cx43)含量的影响。方法:45只SD大鼠随机分为假手术(sham)组、缺血再灌注(IRI)组、缺血预适应(IPC)组、二氮嗪预处理(DPC)组和5-羟葵酸(5-HD)预处理组,每组9只。建立大鼠在体心肌MIRI模型,连接Medlab生物信号采集处理系统,监测左心室收缩压、舒张末压等心功能指标的变化。再灌注结束后,采取血浆检测心肌酶谱,留取心室肌标本,应用Western Blot法检测Cx43含量。结果:DPC组与IRI组比较,肌酸激酶同工酶及乳酸脱氢酶均下降(P0.05~P0.01);Cx43含量的平均光密度显著升高,且以PCx43为主(P0.01);左心室收缩和舒张功能均较IRI组升高(P0.05~P0.01)。结论:DPC能维持再灌注心肌Cx43的数量,降低心肌损伤,维护左心室收缩和舒张功能水平,提示Cx43可能参与了二氮嗪预处理的心肌保护作用。Abstract: Objective: To observe the protective effect of diazoxide preconditioning on rat myocardial ischemia-reperfusion injury in vivo and observe the effect of diazoxide preconditioning on connexin 43 (Cx43) .Methods: Forty-five male SD rats were randomly divided into five groups: sham group, IRI group, IPC group,DPC group and 5-HD group,9 rats in each group.Myocardial ischemiareperfusion injury model was established by ligation of left anterior descending coronary artery for 30 minutes, followed by 120 minutes of reperfusion.The left ventricular systolic pressure, left ventricular diastolic pressure and other heart function were measured by Medlab biological signal collecting and processing system.After reperfusion,myocardial enzymes in plasma were tested; and then the expressions of TCx43 and PCx43 of ischemia-reperfusion myocardium were studied by western blot.Results: Compared with IRI group, the levels of CK-MB and LDH were decreased with significant statistical difference in DPC group(P0.05-P0.01) ; the expression level of Cx43 protein was significantly higher, especially of PCx43(P0.01) ; and left ventricular systolic and diastolic function were increased (P0.05-P0.01) .Conclusions: Diazoxide preconditioning can effectively retain the expression level of Cx43 of left ventricular myocardium caused by ischemia-reperfusion, reduce myocardial injury, and maintain systolic and diastolic function of left ventricle.Cx43 may be involved in the protective effect of diazoxide preconditioning.