激活PPARα表达对AngⅡ诱导的心肌细胞肥大及NFATc4与p65-NFκB相互作用的影响  

Effects of PPARα activation on AngⅡ-induced cardiomyocyte hypertrophy and interaction of NFATc4 with p65-NFκB

作　　者：邹剑[1] 周后凤[1] 先志伟[1] 刘培庆[2] 

机构地区：[1]成都市第五人民医院药剂科,四川成都611130 [2]中山大学药学院药理与毒理学实验室,广东广州510006

出　　处：《中国病理生理杂志》2014年第6期1017-1022,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30772576;No.81273499;No.8107264)

摘　　要：目的:研究PPARα激动剂非诺贝特(fenofibrate)对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大的影响及机制。方法:在AngⅡ诱导的心肌细胞肥大模型中加入非诺贝特(10μmol/L)预处理1 h后,采用real-time PCR检测肥大标志物ANF、BNP和β-MHC mRNA水平变化,Western blotting检测NFATc4和p65-NFκB核转位的变化,免疫共沉淀检测心肌细胞核内p65-NFκB与NFATc4之间的相互作用,EMSA检测NFATc4在BNP启动子上DNA结合活性的变化。结果:非诺贝特可显著抑制AngⅡ诱导的心肌细胞肥大。非诺贝特可抑制AngⅡ诱导的NFATc4和p65-NFκB的入核,以及两者在核内的相互作用。非诺贝特可抑制AngⅡ诱导的NFATc4在BNP启动子上DNA结合活性的增加。结论:非诺贝特可增强心肌细胞核内PPARα与NFATc4之间的相互作用,并减弱p65-NFκB与NFATc4之间的相互结合,进而降低NFATc4在BNP启动子上的DNA结合活性,这可能是其抑制AngⅡ诱导的心肌肥大的重要机制。AIM： To investigate the effects of fenofibrate on angiotensin Ⅱ （ AngⅡ）-induced cardiomyocyte hypertrophy .METHODS：Primary neonatal cardiomyocytes were pretreated with fenofibrate （10μmol/L） for 1 h followed by stimulation with AngⅡ（100 nmol/L）.The mRNA levels of ANF, BNP and β-MHC were measured by real-time PCR. Western blotting was employed to determine the nuclear translocations of NFATc 4 and p65-NFκB.Co-immunoprecipitation was used to investigate the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes .In addition, the DNA binding activity of NFATc4 on the BNP promoter was determined by EMSA .RESULTS：Fenofibrate significantly inhibited AngⅡ-induced cardiomyocyte hypertrophy .Fenofibrate treatment inhibited the nuclear translocations of NFATc 4 and p65-NFκB, as well as the interactions of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes induced by AngⅡ.Fenofi-brate inhibited the binding activity of NFATc 4 with the BNP promoter , which was strengthened by AngⅡ.CONCLU-SION：Fenofibrate enhances the interaction of NFATc 4 with PPARα, decreases the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes , and inhibits the DNA binding activity of NFATc 4 induced by AngⅡ, which may be the important mechanisms of fenofibrate on inhibiting cardiac hypertrophy .

关 键 词：血管紧张素Ⅱ 心肌细胞肥大 PPARΑ NFATc4 p65-NFκB 

分 类 号：R363[医药卫生—病理学]