促红细胞生成素对急性心肌梗死大鼠心脏的保护作用及抗凋亡信号机制  

The cardio-protective effects of erythropoietin on rats during acute myocardial infarction through regulating anti-apoptotic signaling pathways

作　　者：赵玉伟[1] 李法琦[1] 李万玉[2] 周平[1] 邱炯[1] 黄妍[1] 

机构地区：[1]重庆医科大学附属第一医院老年科心血管病组,重庆400016 [2]重庆医科大学药学院药剂学教研室

出　　处：《中国老年学杂志》2013年第4期849-851,共3页Chinese Journal of Gerontology

基　　金：重庆市自然科学基金资助项目(No.CSTC;2007BB5294)

摘　　要：目的探讨促红细胞生成素(EPO)对急性心肌梗死(AMI)大鼠心肌梗死面积、细胞凋亡和磷酸化Akt(p-Akt)蛋白表达的影响。方法 24只雄性SD大鼠,按随机数字表法分为假手术组、AMI组和EPO组(每组8只),用结扎左冠状动脉前降支方法制作大鼠AMI模型,EPO组同时给予5 000 U/kg重组人EPO(rhEPO)腹腔内注射。建模24 h后摘取心脏标本分别用TTC染色检测心肌梗死面积、TUNEL法检测心肌细胞凋亡、Western印迹分析检测心肌组织中p-Akt蛋白表达的变化。结果与假手术组比较,AMI组和EPO组心肌梗死区/左心室质量比值均显著增加〔(0.00±0.00)%vs(21.73±4.14)%和(17.95±2.66)%,P均<0.01〕,但与AMI组比较,EPO组心肌梗死区/左心室质量比值明显降低(P<0.05);与假手术组比较,AMI组和EPO组心肌细胞凋亡指数均显著增加〔(0.51±0.08)%vs(29.62±3.02)%和(21.37±2.39)%,P均<0.01〕,但与AMI组比较,EPO组心肌细胞凋亡指数显著减少(P<0.01)。p-Akt蛋白在三组心肌组织中均有表达,但与假手术组比较,AMI组心肌组织p-Akt蛋白表达显著减少,仅为假手术组的41%(P<0.01);与AMI组比较,EPO组心肌组织p-Akt蛋白表达显著增多,比AMI组升高1.7倍(P<0.01)。结论 EPO干预通过明显缩小AMI大鼠的心肌梗死面积和显著减少心肌细胞凋亡发挥心脏保护作用,其机制可能与上调p-Akt蛋白表达激活Akt抗细胞凋亡信号通路有关。Objective To probe the effect of erythropoietin(EPO) intervention on the infarct size and apoptotic cardiac cells in acute myocardial infarction(AMI) rat models as well as the change of phosphorylated Akt(p-Akt) protein expression in the heart of rats.Methods 24 male SD rats were divided into 3 groups at random: sham-operated,AMI and EPO groups.Rat models of AMI were founded by ligating left anterior descending coronary artery.AMI rats in EPO group were treated at same time with intraperitoneal injection of recombinant human EPO(rhEPO,5 000 U/kg).The infarct size and apoptotic cardiomyocytes in the heart of rats 24 h after AMI were tested by TTC staining and terminal-deoxynucleotidyl transferase-mediated dUTP nick end labe1ing(TUNEL) respectively.The expression of p-Akt protein was determined by Western blot assay.Results Compared with the sham-operated group,the ratio of infarct tissue weight in the left ventricle/whole left ventricular weight and apoptotic cardiomyocytes in the heart of rats in AMI group and EPO group were increased significantly(all P < 0.01).The ratio of infarct tissue weight in the left ventricle/whole left ventricular weight and apoptotic cardiac cells in the heart of rats in EPO group were remarkably reduced compared to AMI group(all P < 0.01).The p-Akt protein was expressed in all hearts of rats in the 3 groups,but the amount of p-Akt protein expression was different in rats among 3 groups.The p-Akt protein expression was decreased significantly in AMI group compared to sham-operated group(P < 0.05).Compared with AMI group,the expression of p-Akt protein was remarkably upregulated in EPO group(P < 0.01).Conclusions EPO treatment can significantly reduce cardiac myocyte apoptosis and infarct size in AMI rat models and remarkably upregulate the expression of p-Akt protein during AMI,which suggests that EPO have an important role in the cardio-protection through modulating Akt cellular signal pathway.

关 键 词：促红细胞生成素 急性心肌梗死 心肌细胞凋亡 Akt 

分 类 号：R363.2[医药卫生—病理学]