坎地沙坦通过抑制ERKs信号通路改善机械刺激诱导的心肌细胞肥大  

Candesartan reversed myocardial hypertrophy induced by mechanical stretch through inhibiting the phosphorylation of ERKs

作　　者：裘琳[1] 刘异[1] 李娟[1] 刘东[1] 郑恒[1] 周宁[2] 杜光[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院心内科,湖北武汉430030

出　　处：《中国医院药学杂志》2014年第12期994-997,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金(编号:81100087)

摘　　要：目的:探讨坎地沙坦改善机械刺激诱导的心肌细胞肥大的效应及机制。方法:体外培养新生大鼠心肌细胞,接种在特制的硅胶皿上。按数字编码随机分为对照组、机械刺激组和机械刺激+坎地沙坦干预组。牵张硅胶皿(延伸120%)30 min构建机械刺激诱导的心肌细胞肥大模型,以3 H掺入法检测各组心肌细胞蛋白合成率,α-MHC免疫荧光染色以激光共聚焦成像测算心肌细胞表面积。以Real-time PCR和Western-Blot检测心肌细胞中心房利钠肽(ANP),骨骼肌α-肌动蛋白(SAA)基因和磷酸化细胞外调节蛋白激酶(ERKs)表达变化。结果:坎地沙坦显著改善了机械刺激所致的心肌细胞表面积(1.78±0.13 vs 3.16±0.28,P<0.05)和蛋白合成率(4.15±0.44 vs 6.75±0.71,P<0.05)增加以及ANP(2.21±0.27 vs 4.1±0.93,P<0.05)和SAA(5.45±0.6 vs 7.4±1.43,P<0.05)的表达上调,也显著降低了机械刺激诱导的ERKs磷酸化(3.85±0.33 vs 6.68±0.86,P<0.05)。结论:坎地沙坦可通过抑制ERKs磷酸化改善机械刺激诱导的心肌细胞肥大反应。OBJECTIVE To evaluate the inhibitory effect of candesartan on myocardial hypertrophy induced by mechanical stress in vitro and to study on the mechanism of action involved.METHODS Neonatal rat cardiomyocytes were isolated and cultured in silica-gel plates in vitro.All the cardiomyocytes were divided into three groups：control group,mechanical stretched-group,and mechanical stretch plus candesartan group.Cardiomyocytes cultured in the silicon plates were stimulated by mechanical stretch to 120%for 30 min to establish myocardial hypertrophy.The protein synthesis and surface area of cardiomyocytes were detected by 3 H leucine incorporation and immunofluorescence ofα-MHC.Realtime-PCR was used to measure the reprogramming of atrial natriuretic peptide（ANP）and skeletalα-actin（SAA）,and Western-blot was used to detect the phosphorylation of extracellular regulated protein kinases（ERKs）.RESULTS Pretreatment with candesartan reversed mechanical stretch-induced increases in protein synthesis and cell size,as well as the mRNA expression of ANPand SAAand ERKs phosphorylation.CONCLUSION Candesartan significantly inhibited mechanical stretch-induced myocardial hypertrophy which partly attributed to the inhibitory effect of candesartan on ERKs phosphorylation.

关 键 词：坎地沙坦 机械刺激 心肌肥大 细胞外调节蛋白激酶 

分 类 号：R963[医药卫生—微生物与生化药学]