PPAR-α参与血管紧张素Ⅳ诱导的心肌细胞肥大

基础医学与临床 ›› 2011, Vol. 31 ›› Issue (10): 1094-1098.

PPAR-α参与血管紧张素Ⅳ诱导的心肌细胞肥大

陈加飞¹,王全华²,²,吴芹²,²,王平²,³,蒋青松⁴

1. 重庆医科大学药理教研室
2.
3. 重庆科瑞制药有限责任公司研究所
4. 重庆医科大学药理学教研室

收稿日期:2010-11-29 修回日期:2010-12-29 出版日期:2011-10-05 发布日期:2011-10-08
通讯作者: 蒋青松 E-mail:cqjiangqs@yahoo.cn
基金资助:
重庆市自然科学基金

PPAR-α involves in cardiomyocyte hypertrophy induced by angiotensin Ⅳ

Received:2010-11-29 Revised:2010-12-29 Online:2011-10-05 Published:2011-10-08

摘要/Abstract

摘要： 摘要：目的研究过氧化物酶体增殖物激活受体-α（peroxisome proliferator-activated receptor-α，PPAR-α）在血管紧张素Ⅳ（angiotensin Ⅳ，Ang Ⅳ）诱导心肌细胞肥大中的作用。方法利用乳鼠心肌细胞培养，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，观察不同浓度的Ang Ⅳ对心肌细胞的作用，并观察PPAR-α激动剂非诺贝特（fenofibrate，FF）和阻断剂MK886对Ang Ⅳ作用的影响；利用Real-time PCR和Western blot方法检测mRNA及蛋白水平的表达。结果 Ang Ⅳ浓度依赖地（0.01、0.1、1 nmol/L）诱导心肌细胞肥大；同时PPAR-α mRNA和蛋白表达明显降低（P <0.01）；FF明显地抑制Ang Ⅳ 1 nmol/L诱导的心肌细胞肥大（P <0.01），并上调PPAR-α mRNA和蛋白表达（P <0.01）。MK886可完全取消FF的上述作用（P <0.05）。结论 Ang Ⅳ所致心肌肥大与PPAR-α信号通路受损有关。

关键词: 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

Abstract: Abstract: 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 significantly. FF at 0.3 μmol/L increased the expressions of PPAR-α both mRNA and protein (P <0.01). All of these effects of FF could be abolished by MK886 at 0.3 μmol/L (P<0.05). Conclusion: PPAR-α signal transduction pathway involves in cardiomyocyte hypertrophy induced by Ang Ⅳ.

Key words: Key words: Angiotensin Ⅳ, Peroxisome proliferator-activated receptor-α, Cardiomyoeyte hypertrophy

中图分类号:

R123.1

陈加飞王全华吴芹王平蒋青松. PPAR-α参与血管紧张素Ⅳ诱导的心肌细胞肥大[J]. 基础医学与临床, 2011, 31(10): 1094-1098.