Objective To evaluate the effects of valsartan on myocardial no-reflow after ische-mia-reperfusion in rats ,and to investigate the signal transduction mechanism .Methods Fifty-six male SD rats were randomly assigned to four groups :control group (n=8) ,ischemia and reperfusion group (n=16 ) ,valsartan group(10 mg · kg ,n=16),and valsartan+LY294002 group(val-sartan 10 mg · kg ,LY294002 0 .3 mg · kg ,n= 16 ) .After acclimatization for 1 week ,the left anterior descending coronary artery was occluded for 60 minutes and reperfused for 120 minutes to establish myocardial ischemia-reperfusion no-reflow model. Valsartan (10 mg · kg ) and LY294002(0 .3 mg · kg ) were administered via tail vein 15 and 5 minutes before reperfusion , respectively .After reperfusion ,myocardial no-reflow zone and ischemic area were observed using Thioflavin S and Evans blue staining and myocardial infarct size was measured using triphenyltet -rnrazolium chloride (TTC) staining .The levels of serum creatine kinase isoenzyme (CK-MB) were detected after treatment . The expression of Akt , p-Akt ,p-eNOS and eNOS was determined by western blotting .Results Compared with ischemia and reperfusion group ,valsartan increased the expression of p-Akt and p-eNOS ( P<0 . 01 ) , reduced no-reflow area [(31 . 26 ± 2 . 83 )% vs (21.60 ± 3.29)% ,P<0 .01], and decreased infarct size[(40 .16 ± 4 .19 )% vs (27.93 ± 4.57)% , P<0.01]. However,these effects were reversed by LY 294002 ( P<0 .01) .Conclusion Valsartan can reduce myocardial no-reflow area and infarct size after ischemia-reperfusion via PI3K-Akt-eNOS signal transduction pathway .%目的 观察缬沙坦后处理对大鼠心肌缺血再灌注损伤后无复流的影响,并探讨其信号转导的可能机制.方法 56只雄性SD大鼠按随机数字表法分为4组:对照组(n=8),缺血再灌注(ischemia reperfusion,I/R)组(n=16),缬沙坦组(n=16,缬沙坦10 mg·kg-1),缬沙坦+LY294002组(n=16,缬沙坦10 mg·kg-1、LY294002 0.3 mg·kg-1).大鼠适应性喂养1周后,结扎冠状动脉左前降支(LAD) 60 min再灌注120 min,制作大鼠心肌缺血再灌注无复流模型.缬沙坦于再灌注前15 min经尾静脉注射,LY294002于再灌注前5 min经尾静脉注射.再灌注结束后,采用硫磺素S、伊文思蓝活体染色,观察大鼠心肌无复流范围及缺血面积;氯化三苯基四氮唑(TTC)染色评估大鼠心肌梗死面积;测血清肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB);免疫印迹法(western blot)测定缺血心肌蛋白激酶B(protein kinase B,Akt)、磷酸化蛋白激酶B(phosphorylated akt,p-Akt)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)和磷酸化内皮型一氧化氮合酶(phosphorylated eNOS,p-eNOS)的蛋白表达.结果 与I/R组相比,缬沙坦组的无复流面积减少[(31.26±2.83)% 比 (21.60±3.29)%,P＜0.01],梗死面积减少[(40.16±4.19)% 比 (27.93±4.57)%,P＜0.01],Akt、eNOS的磷酸化程度增高(P＜0.01);缬沙坦联合应用LY294002后,该组与缬沙坦组相比,其无复流面积及梗死面积均有增加(P＜0.01).结论 缬沙坦可以明显减少大鼠心肌缺血再灌注后无复流面积和梗死面积,其作用机制可能与磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/Akt/eNOS信号转导途径的激活有关.
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