中文摘要：

目的研究过氧化物酶体增殖物激活受体-γ（PPAR-γ）激活对心肌纤维化的影响是否与血管紧张素Ⅱ（Ang11）-Ets-1通路有关。方法体外培养大鼠心脏成纤维细胞（CFs），分为对照组、AngⅡ组、AngⅡ＋不同浓度rosigli—tazone处理组、Angll＋不同PPAR-γ激动剂组、AngⅡ＋不同PPAR-1拮抗剂组，采用实时定量RT—qPCR、Westernblot等检测Ets-1、CTGFmRNA及蛋白表达，并测定TGF-B1和Smad2／3的表达及磷酸化水平。结果在CFs中，AngⅡ诱导Ets-1mRNA及蛋白表达（P〈0．05），上调Ets-1下游靶基因CTGF的蛋白的表达（P〈0．05），增加TGF-β1和Smad2／3的表达及磷酸化（P〈0．05）。PPAR-γ激动剂rosiglitazone，15d-PGJ2抑制AngⅡ诱导的Ets-1mRNA及蛋白的表达（P〈0．05），下调Ang11诱导的CTGF蛋白表达（P〈0．05），部分阻断AngⅡ诱导的TGF-β1的表达、Smad2／3的表达及磷酸化（P〈0．05）。PPAR-γ拮抗剂GW9662及BADGE均可阻断rosiglitazone对Ets-1及CTGF表达的抑制作用（P〈0．05）。结论PPAR-1激活主要通过TGF-β1／Smad2／3通路介导抑制Ang1I诱导的大鼠CFs转录因子Ets-1的过表达。

英文摘要：

Objective To investigate whether peroxisome proliferator-activated receptor-γ （PPAR-γ） activation in- hibits cardiac fibrosis through the angiotensin Ⅱ （Ang Ⅱ）-Ets-1 pathway. Methods Primary cultured cardiac fi- broblasts （CFs） of rats were divided into these groups： control, Ang Ⅱ, Ang Ⅱ ＋ rosiglitazone, Ang Ⅱ ＋ other PPAR-γligands, Ang Ⅱ ＋ PPAR-γantagonists. The change in expression of Ets-1, connective tissue growth factor （CTGF）, transforming growth factor （TGF）-β1 and Smad2/3 was assessed by using real-time RT-PCR and west- ern blot. Results In growth-arrested CFs, Ang Ⅱ induced the expression of Ets-1 mRNA and protein（P 〈 0.05）, up-regulated expression of Ets- 1 down stream target CTGF （P 〈 0.05 ） , enhanced the expression of TGF-β1 and the expression and phosphorylation of Smad2/3 （P 〈 0.05 ）. PPAR-γ ligands rosiglitazone and 15d-PGJ2 attenuated the expression of Ang Ⅱ-induced Ets- 1 mRNA and protein （P 〈 0. 05）, decreased the induction of CTGFby Ang Ⅱ （ P 〈 0.05 ） , inhibited expression of TGF-β1 duced by Ang Ⅱ （P 〈 0. 05 ）. These suppressive effects nists GW9662 and BADGE （ P 〈 0. 05 ）. Conclusions pression via the TGF-151/Smad2/3 signaling pathway. and the expression and phosphorylation of Smad2/3 in- on Ets-1 and CTGF were attenuated by PPAR-γ antago- Activation of PPAR-~ inhibits Ang Ⅱ-induced Ets-1 ex-pression via the TGF-β1/Smad2/3 signaling pathway.