依那普利拉抗心肌成纤维细胞增殖的分子机制

J4 ›› 2009, Vol. 35 ›› Issue (4): 591-594.

依那普利拉抗心肌成纤维细胞增殖的分子机制

孙红霞^1,2, 杨世杰¹

1.吉林大学基础医学院药理学教研室|吉林长春130021；2.北华大学药学院药理学教研室|吉林吉林132013

收稿日期:2008-11-06 出版日期:2009-07-28 发布日期:2009-08-24
通讯作者: 杨世杰 E-mail:jcyaoli@sina.com
作者简介:孙红霞（1965-）|女|吉林省吉林市人|教授|医学博士|主要从事心血管分子药理学的研究。
基金资助:
国家自然科学基金资助课题（30672654）

Effects of enalaprilat on proliferation of cardiac fibroblasts and molecular

SUN Hong-Xia^1,2, YANG Shi-Jie¹

1.Department of Pharmacology,School of Basic Medical Sciences,Jilin University,Changchun 130021,China；2. Department of Pharmacology,School of Pharmacy,Beihua University,Jilin 132013,China

Received:2008-11-06 Online:2009-07-28 Published:2009-08-24

摘要/Abstract

摘要：

目的：观察血管紧张素转换酶抑制剂（ACEI）依那普利拉（Ena）和蛋白激酶C（PKC）抑制剂白屈菜红（Chele）对血管紧张素Ⅱ（AngⅡ）诱导的新生鼠心肌成纤维细胞（CFb）增殖、细胞周期、Ⅰ型胶原纤维（collagen Ⅰ）、PKC和细胞周期蛋白cyclinD₁蛋白表达的影响，阐明Ena抗CFb增殖的分子机制。方法：培养的新生Wistar大鼠CFb分为对照组、AngⅡ组、Chele+AngⅡ组、Chele+AngⅡ＋Ena组和AngⅡ＋Ena组，采用胰酶消化、差速贴壁法培养CFb，四氮唑盐（MTT）比色法检测细胞增殖；免疫细胞化学染色（IC）法测定collagen Ⅰ含量；流式细胞术（FCM）检测细胞周期；免疫印迹法检测PKC和细胞周期蛋白cyclinD₁表达。结果：与AngⅡ组比较，Chele和Ena组及Chele+AngⅡ＋Ena组CFb增殖率均显著降低（P<0.05或P<0.001）,collagen Ⅰ含量降低（P<0.05或P<0.01）,CFb G₀/G₁期细胞百分率升高,S期细胞百分率降低（P<0.05　或P<0.01）,PKC和cyclinD₁蛋白表达水平降低（P<0.05或P<0.01）。结论：Ena和Chele能抑制AngⅡ诱导的CFb增殖和胶原蛋白分泌，其机制可能是通过抑制PKC-cyclinD₁转导通路实现的。

关键词: 依那普利拉；白屈菜红；cyclinD₁；心肌成纤维细胞

Abstract:

Abstract:Objective To observe the effects of ACE inhibitor enalaprilat(Ena) and protein kinase C(PKC) inhibitor chelerythrine(Chele)on proliferation,collagen Ⅰ,cell cycle,PKC and cyclinD₁protein expression of neonatal cardiac fibroblasts(CFb) and to probe its molecular mechanism.Methods CFb of neonatal Wistar rats were divided into control group,AngⅡ group,Chele+AngⅡ group,Chele+AngⅡ+Ena group and AngⅡ+Ena group.CFb were isolated by trypsin digestion method.MTT colorimetric assay was adopted to evaluate cell proliferation,immunocytochemical staining(IC) was used to measure collagen Ⅰ content,Western blotting and flow cytometry were used to detect PKC,cyclinD₁and cell cycle respectively.Results Compared with AngⅡ group，the MTT value decreased dramatically（P<0.05 or P<0.001）,collagen Ⅰ content decreased（P<0.05 or P<0.01）;the percentage of cell at G₀/G₁ phase increased and the percentage of cells at S phase decreased（P<0.05 or P<0.01）;and the PKC and cyclinD₁ protein expressions were inhibited in Chele,Ena,and Chele+AngⅡ+Ena groups（P<0.05 or P<0.01）.Conclusion The antiproliferation effects of Ena on CFb can be attributed to inhibiting PKC/cyclinD₁ signal pathway possibly.

Key words: enalaprilat;chlerythrine;cyclinD₁;cardiac fibroblast

中图分类号:

R542.2

孙红霞, 杨世杰. 依那普利拉抗心肌成纤维细胞增殖的分子机制[J]. J4, 2009, 35(4): 591-594.

SUN Hong-Xia, YANG Shi-Jie. Effects of enalaprilat on proliferation of cardiac fibroblasts and molecular[J]. J4, 2009, 35(4): 591-594.