PHD2/HIF-1α介导β-AR调控大鼠心梗后心力套竭  

Mechanism of β-AR regulating PHD2/HIF-1α pathway participating in heart failure after myocardial infarction in rats

作　　者：张本凯 王政 朱峰 汪和贵[1] Zhang Benkai;Wang Zheng;Zhu Feng;Wang Hegui(Department of Cardiology,Yijishan Hospital of Wannan Medical College,Wuhu Anhui 241001,China)

机构地区：[1]皖南医学院附属弋矶山医院心血管内科,安徽芜湖241001

出　　处：《中华急诊医学杂志》2020年第2期239-242,共4页Chinese Journal of Emergency Medicine

基　　金：安徽省自然科学基金(1308085MH116);安徽省高校自然科学研究重大项目(KJ2015ZD42);皖南医学院弋矶山医院引进人才项目(YR201615)。

摘　　要：目的观察PHD2、HIF-1α在心肌梗死后心衰时表达量的变化,探讨β肾上腺受体(β-AR)调控PHD2/HIF-1α通路对心肌梗死后心衰发生影响。方法采用冠状动脉左前降支结扎法制备大鼠急性心梗模型,实验分为3组:假手术组、模型组、普蔡洛尔组。记录冠脉结扎前后心电图变化,12周后利用心脏超声检测心功能变化,PCR和Western Blot检测PHD2、HIF-1α的mRNA及蛋白表达的变化。结果结扎冠脉后心电图示ST段显著抬高。结扎12周后心脏射血分数(Ejection fraction,EF)从假手术组的(79.45±2.86)%下降到模型组的(61.10±2.78)%(P<0.05),普蔡洛尔组则高于模型组为(67.33±2.66)%(P<0.05)。PHD2的mRNA及蛋白表达在模型组显著下降(P<O.05),而普蔡洛尔组较模型组明显上升(P<O.05)。HIF-1α的mRNA及蛋白表达在模型组显著上升(P<0.05),而普蔡洛尔组较模型组明显下降(P<0.05)。结论PHD2/HIF-1α通路在大鼠心梗后心衰的发生过程中可能具有重要作用;而心肌梗死后B-肾上腺系统激活,可能通过对PHD2/HIF-1α通路的调节进而促进心衰的发生。Objective To observe expression changes of PHD2 and HIF-1α,and to investigate the effect of β-AR on the regulation of PHD2/HIF-1α pathway on heart failure after myocardial infarction.Methods Acute myocardial infarction model in rats were established by ligation of left anterior descending coronary artery.The experiment was randomly(random number)divided into three groups:sham operation group,model group and propranolol group.The changes of electrocardiogram before and after coronary artery ligation were recorded,and cardiac function was detected by echocardiography 12 weeks later.Also,the mRNA and protein expression of PHD2 and HIF-1α were detected by PCR and Western Blot.Results The ST segment of the ECG showed a significant elevation after the coronary artery was ligated.After 12 weeks of ligation,compared with model group,the ejection fraction(EF)in sham operation group[(79.45±2.86)%vs(61.10±2.78)%,P<0.05]and in propranolol group was higher[(67.33±2.66)%vs(61.10±2.78)%,P<0.05].The mRNA and protein expression of PHD2 decreased significantly in the model group(P<0.05),while the propranolol group increased significantly compared with the model group(P<0.05).The mRNA and protein expression of HIF-1α increased significantly in the model group(P<0.05),while the propranolol group decreased significantly compared with the model group(P<0.05).Conclusions PHD2/HIF-1α pathway may play an important role in the development of heart failure after myocardial infarction in rats.Activation of β-adrenal system after myocardial infarction may promote the occurrence of heart failure by regulating PHD2/HIF-1α pathway.

关 键 词：β肾上腺受体(β-AR) 脯氨酰瓮化酶2(PHD2) 缺氧诱导因子1α(HIF-1α) 心机梗死 心力衰竭 冠状动脉 心电图 射血分数(EF) 

分 类 号：R542.22[医药卫生—心血管疾病] R541.6[医药卫生—内科学]