PPAR-α参与血管紧张素Ⅳ诱导大鼠心肌细胞肥大  

PPAR-α involves in cardiomyocyte hypertrophy induced by angiotensin Ⅳ in rats

作　　者：陈加飞[1] 王全华[1] 吴芹[2] 王平 蒋青松[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆400016 [2]遵义医学院药理教研室,贵州遵义563003 [3]重庆科瑞制药有限责任公司研究所,重庆400060

出　　处：《基础医学与临床》2011年第10期1094-1098,共5页Basic and Clinical Medicine

基　　金：高等学校博士学科点专项科研基金(20105503120005)

摘　　要：目的研究过氧化物酶体增殖物激活受体-α(PPAR-α)在血管紧张素Ⅳ(AngⅣ)诱导大鼠心肌细胞肥大中的作用。方法用乳鼠心肌细胞,以细胞表面积、蛋白含量和心房利钠因子mRNA表达为心肌肥大指标,观察不同浓度AngⅣ对心肌细胞的作用,并观察PPAR-α激动剂非诺贝特(FF)和阻断剂MK886对AngⅣ作用的影响;用Real-time PCR和Western blot方法检测mRNA及蛋白水平的表达。结果 AngⅣ浓度依赖地(0.01、0.1及1 nmol/L)诱导心肌细胞肥大;使PPAR-αmRNA和蛋白表达明显降低,分别为55.7±9.6和3.3±0.3(P<0.01);FF明显抑制AngⅣ1 nmol/L诱导的心肌细胞肥大(P<0.01),上调PPAR-αmRNA和蛋白表达,分别增加至151.7±10.5和6.7±0.7(P<0.01)。MK886可完全取消FF的上述作用(P<0.05)。结论 AngⅣ所致心肌肥大与PPAR-α信号通路受损有关。Objective To study the role of peroxisome proliferator-activated receptor-α（PPAR-α） signal transduction pathway in cardiomyocyte hypertrophy induced by angiotensin Ⅳ（Ang Ⅳ）.Methods The cardiomyocyte hypertrophic responses were assayed by measuring the cell surface area,protein content,and atrial natriuretic factor（ANF） mRNA expression.In cultured cardiomyocytes,fenofibrate（FF）,a selective PPAR-α agonist,and MK886,a selective PPAR-α antagonist,were used to investigate the mechanisms of Ang Ⅳ.The expressions of mRNA and protein were assayed by Real-time PCR and Western blot,respectively.Results In cultured cardiomyocytes,Ang Ⅳ（0.01,0.1,1 nmol/L） can induce cardiomyocyte hypertrophy in a concentration-dependent manner.Meanwhile,the expressions of PPAR-α mRNA and protein decreased to 55.7 ± 9.6 and 3.3±0.3,respectively（P0.01）.FF at 0.3 μmol/L up-regulated the expressions of PPAR-α both mRNA and protein,increased to 151.7 ± 10.5 and 6.7±0.7,respectively（P0.01）.All of these effects of FF could be abolished by MK886 at 0.3 μmol/L（P0.05）.Conclusions PPAR-α signal transduction pathway involves in cardiomyocyte hypertrophy induced by Ang Ⅳ.

关 键 词：血管紧张素Ⅳ 过氧化物酶体增殖物激活受体-Α 心肌肥大 

分 类 号：R541[医药卫生—心血管疾病]