缬沙坦对心肌缺血再灌注损伤的保护作用

Cardioprotection of valsartan on cardiac ischemic-reperfusion injury

目的用兔在体心肌缺血再灌注模型研究缬沙坦(valsartan)后处理对缺血再灌注心肌的保护作用及其机制。方法兔24只,随机分为3组,对照组:结扎冠状动脉前降支1h,再灌注5h;后处理组:处理同对照组外,于再灌注前15min耳缘静脉注射缬沙坦,剂量30mg/kg;缬沙坦组:处理同后处理组外,在再灌注前5min耳缘静脉注射磷酸肌醇3激酶抑制剂LY294002(0.3mg/kg)。分别于再灌注3h和5h取兔血,测定各组血超氧化物歧化酶(superoxidedismutase,SOD)和丙二醛的水平。实验终末,取结扎部位心肌进行免疫组化处理,观察心肌组织蛋白激酶B和内皮型一氧化氮合酶(endothelialnitricoxidesynthase,eNOS)含量以及心肌组织结构的变化。结果后处理组血SOD含量高于其它组(P<0.01),丙二醛含量低于其它组(P<0.01),后处理组心肌组织蛋白激酶B和eNOS含量明显高于其它组(P<0.01);其余组间各项观察指标无显著差异。结论缬沙坦后处理对缺血再灌注心肌具有保护作用,其作用可能是通过再灌注损伤清除激酶信号转导通路来实现的。

Objectives To study whether valsartan postconditioning(PostC) have protective effects on cardiac ischemic-reperfusion injury and the probable mechanism.Methods All rabbits were subjected to a total of 60 minutes of left coronary artery occlusion(LCAO) and 5 hours of reperfusion.The rabbits were randomized to one of three groups:① Control:LCAO and 5-hour-reperfusion;② PostC:after 45 minutes of LCAO,rabbits were received 30 mg/kg IV of valsartan,the other steps follow control group;③Drug:rabbits were received 30 mg/kg IV of valsartan and 0.3 mg/kg IV of the PI3K antagonist LY294002 at the time of 45 min and 55 min of LCAO respectively,the other steps follow control group.Blood SOD and MDA were measured at the time of 3-hour and 5-hour reperfusion.Myocardium Akt and eNOS were tested by immunohistochemistric methods.The tissue structures were observed by microscope.Results The levels of SOD were higher and MDA were lower in the PostC than in the other groups.The quantity of Akt and eNOS in myocardium were higher in the PostC than in the other groups.While there were no differences about all indexes between other groups.Conclusions Valsartan postconditioning(PostC) has protective effects on cardiac ischemic-reperfusion injury and the probable mechanism is RISK pathway.