氯沙坦介导SERCA2a蛋白抑制心肌细胞凋亡缓解心肌梗死后心力衰竭大鼠的心肌损伤  

Losartan-mediated SERCA2a protein inhibits cardiomyocyte apoptosis and relieves myocardial injury in rats with heart failure after myocardial infarction

作　　者：黄莹[1] 王飞[2] 刘春茹[1] 周南 于洋 HUANG Ying;WANG Fei;LIU Chun-ru;ZHOU Nan;YU Yang(Department 1,Cadre Internal Medicine,Tieling Central Hospital,Tieling,Liaoning 112000;Department 1,Department of Neurology,Tieling Central Hospital,Tieling,Liaoning 112000;Department of Anesthesiology,General Hospital of Northern Theater Command,Shenyang,Liaoning 110000,China)

机构地区：[1]铁岭市中心医院干部内科一病房,辽宁铁岭112000 [2]铁岭市中心医院神经内科一病房,辽宁铁岭112000 [3]北部战区总医院麻醉科,辽宁沈阳110000

出　　处：《热带医学杂志》2021年第10期1298-1302,1317,共6页Journal of Tropical Medicine

基　　金：辽宁省自然基金(20180551091)。

摘　　要：目的探索氯沙坦对心肌梗死后心力衰竭大鼠心肌损伤的保护作用,探讨SERCA2a蛋白的作用机制。方法 SD大鼠随机分为假手术组(Sham组)、心力衰竭模型组(HF组)、氯沙坦治疗组(Losartan组),每组10只;HF组和Losartan组采用左前降支冠状动脉结扎法制备心力衰竭大鼠模型,成模后给予20 mg/(kg·d)氯沙坦灌胃处理,连续给药14 d。超声检测各组大鼠的心肌功能;检测左心室质量指数;HE染色观察心肌病理组织学损伤;TUNEL检测心肌细胞凋亡;免疫荧光和Western blot检测各组大鼠cleaved caspase-3和SERCA2蛋白的表达;定磷法检测心肌处SERCA 2a活力。结果与Sham组比较,HF组大鼠左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)显著升高,左室收缩期后壁厚度(LVPWDs)、左心室射血分数(LVEF)、左室缩短分数(LVFS)显著降低(P<0.05),左心室质量指数显著升高,心肌细胞凋亡率和cleaved caspase-3蛋白相对表达显著升高,SERCA2 a蛋白相对表达及活力显著降低,差异均有统计学意义(P<0.05);与HF组比较,Losartan组LVEDD、LVESD显著降低,LVPWDs、LVEF、LVFS显著升高,左心室质量指数降低,心肌细胞凋亡率和cleaved caspase-3蛋白相对表达量降低(P<0.05);与模型组比较,Losartan组SERCA2 a蛋白相对表达量显著增加,并且其活力显著增强(P<0.05)。结论 Losartan可以激活SERCA2a蛋白,抑制心肌细胞凋亡,改善心衰大鼠心肌损伤。Objective To explore the protective effect of losartan on myocardial injury in rats with heart failure after myocardial infarction,and explore the mechanism of action of SERCA2 a protein. Methods SD rats were randomly divided into sham operation group(sham),heart failure model group(HF),losartan treatment group(Losartan),10 in each group;HF and Losartan groups were prepared by left anterior descending coronary artery ligation. Rat models of heart failure were given 20 mg/(kg · d) losartan by intragastric administration for 14 days. Ultrasound was used to detect myocardial function and left ventricular mass index. HE staining was used to observe myocardial pathological histological injury. TUNEL was used to detect myocardial cell apoptosis;immunofluorescence and Western blot were used to detect cleaved caspase-3 and SERCA2 protein expression. Phosphorus determination was used to detect SERCA 2 a activity in myocardium. Results Compared with the sham group,the left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter(LVESD)of the HF group were significantly increased,and the posterior wall thickness of left ventricular systole(LVPWDs),left ventricular ejection fraction(LVEF),and left ventricular shortening score(LVFS)were significantly decreased(P<0.05), the left ventricular mass index was significantly increased(P<0.05),cardiomyocyte apoptosis rate and cleared caspase-3 protein relative expression were significantly increased(P<0.05);the relative expression of SERCA2 a protein and its activity was significantly reduced(P<0.05). Compared with the HF group,losartan improved heart function in rats with heart failure;LVEDD and LVESD were significantly reduced;LVPWDs,LVEF,and LVFS were significantly increased(P<0.05);myocardial injury relieved and the left ventricular mass index reduced(P<0.05);cardiomyocyte apoptosis rate and relative expression of cleared caspase-3 protein was significantly reduced(P<0.05). Compared with model group,the relative expression of SERCA2 a was significantl

关 键 词：氯沙坦 心力衰竭 细胞凋亡 SERCA2A 

分 类 号：R541.61[医药卫生—心血管疾病]