«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2011年第1期

页码:

11-15

栏目:

基础研究

出版日期:

2010-10-27

文章信息/Info

Title:

Inhibitory effect of peroxisome proliferator-activated receptor-α agonist on proliferation of cardiac fibroblasts

作者:

赵晓燕¹; 赵连友²; 郑强荪²; 张兴凯¹

1.解放军第五医院心内科，宁夏 银川 750004；2.第四军医大学唐都医院心内科，陕西 西安 710038

Author(s):

ZHAO Xiao-yan¹;  ZHAO Lian-you²;  ZHENG Qiang-sun²;  ZHANG Xing-kai¹

1.Department of Cardiology, PLA Fifth Hospital, Yinchuan 750004, Ningxia, China; 2.Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China

关键词:

过氧化物酶增殖物激活受体α; 非诺贝特; 转化生长因子β1; 糜酶; 心脏成纤维细胞; 增殖

Keywords:

peroxisome proliferator-activated receptor-α;  fenofibrate;  transforming growth factor-β1;  chymase;  cardiac fibroblast;  proliferation

分类号:

R542.23

DOI:

-

文献标识码:

A

摘要:

目的: 探讨过氧化物酶增殖物激活受体α（PPARα）激动剂非诺贝特(fenofibrate)对糜酶介导的大鼠心脏成纤维细胞（CFs）增殖的影响及作用机制。方法： 用胰酶消化法分离、培养新生SD大鼠的CFs。采用3H-脱氧胸腺嘧啶核苷（3H-TdR）掺入法测定CFs的DNA合成，用流式细胞术分析细胞周期，用RT-PCR检测PPARα 及转化生长因子β1（TGF-β1）mRNA的表达。结果： ①以不同浓度的非诺贝特预处理后，CFs的3H-TdR掺入量呈浓度依赖性减少，其中50和100 μmol/L组均较糜酶组明显减少（分别为P<0.05和P<0.01）。②随着非诺贝特浓度的增加，CFs在G0/G1期的百分率逐渐增加，S期的百分率和增殖指数逐渐减少，其中50和100 μmol/L组与糜酶组比较，上述各项指标均有显著性差异（分别为P<0.05和P<0.01）。③以25、50和100 μmol/L非诺贝特预处理后，PPARα mRNA表达的水平呈浓度依赖性增加，其中50和100 μmol/L组均较糜酶组显著增加（分别为P<0.05和P<0.01）。④随着非诺贝特浓度的增加，TGF-β1 mRNA表达水平呈递减趋势，其中50和100 μmol/L组均较糜酶组明显减少（P<0.01）。结论： PPARα 激动剂非诺贝特以浓度依赖的方式抑制糜酶诱导的大鼠CFs增殖的作用，其机制与PPARα基因表达的上调和TGF-β1基因表达的下调有关，提示PPARα 和TGF-β1这两条信号通路可能存在信息交流。

Abstract:

AIM: To investigate the effect of peroxisome proliferator-activated receptor-α (PPARα) agonist fenofibrate on the proliferation of rat cardiac fibroblasts (CFs) induced by chymase and its mechanism of action. METHODS: Cultured CFs from neonatal SD rats were isolated by trypsinization and the DNA synthesis and cellular cycle of the CFs were evaluated, respectively, by 3H-TdR incorporation and flow cytometry. mRNA expressions of PPARα and TGF-β1 in the CFs were determined by RT-PCR. RESULTS: Pretreatment with fenofibrate decreased the 3H-TdR incorporation of the CFs in a concentration-dependent manner. The 3H-TdR incorporations pretreated with 50 and 100 μmol/L fenofibrate were significantly lower than those in the chymase group (P<0.05, P<0.01). Cellular cycle analysis showed that pretreatment with 50 and 100 μmol/L fenofibrate markedly increased the cellular percentage in G0/G1 stage and decreased the cellular percentage in S stage and proliferation index compared with those in the chymase group (P<0.05, P<0.01). Pretreatment with fenofibrate increased the PPARα mRNA and decreased the TGF-β1 mRNA in a dose-dependent manner. PPARα mRNA pretreated with 50 and 100 μmol/L fenofibrate was higher than in the chymase group (P<0.05, P<0.01) and the TGF-β1 mRNA was lower than in the chymase group (P<0.01). CONCLUSION: PPARα agonist fenofibrate inhibits the proliferation of rat CFs induced by chymase possibly through the upregulation of PPARα mRNA and the downregulation of TGF-β1 mRNA, suggesting that there may be cross-talk between the PPARα and TGF-β1 signal pathways.

参考文献/References

[1]王先梅，赵连友，郑强荪，等. 糜酶抑制剂对自发性高血压大鼠心肌纤维化的影响[J]. 心脏杂志, 2006, 18（1）：31-34．

[2]Zhao XY, Zhao LY, Zheng QS, et al. Chymase induces profibrotic response via transforming growth factor-β1/Smad activation in rat cardiac fibroblasts[J]. Mol Cell Biochem, 2008, 310（1-2）：159-166．

[3]Akgul A. Can cardiac fibrosis be prevented? Mast cell inhibition versus anti-chymase activity[J]. Eur J Cardiothorac Surg, 2009, 35（3）：553-554．

[4]赵晓燕，赵连友，郑强荪，等. 糜酶对大鼠心脏成纤维细胞增殖和胶原合成的影响[J]. 心脏杂志, 2008, 20（3）：268-272．

[5]赵晓燕，赵连友，郑强荪，等. 糜酶介导心脏成纤维细胞增殖中转化生长因子-β1的作用[J]. 中华高血压杂志, 2008, 16（5）：455-459．

[6]赵晓燕，赵连友，郑强荪，等. 转化生长因子β1/Smad通路调控糜酶诱导的大鼠心脏成纤维细胞增殖[J]. 心脏杂志, 2010, 22（1）：25-29．

[7]Lebrasseur NK, Duhaney TA, De Silva DS, et al. Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension[J]. Hypertension, 2007, 50（3）：489-496．

[8]吴强，杨永曜，李隆贵，等. 非诺贝特对压力超负荷大鼠心肌细胞凋亡和凋亡相关基因Fas、Fas-L表达的影响[J]. 心脏杂志, 2007, 19（5）：502-504．

[9]Steiner G. Fenofibrate for cardiovascular disease prevention in metabolic syndrome and type 2 diabetes mellitus[J]. Am J Cardiol, 2008, 102（12A）：28L-33L．

[10]Rose M, Balakumar P, Singh M. Ameliorative effect of combination of fenofibrate and rosiglitazone in pressure overload-induced cardiac hypertrophy in rats[J]. Pharmacology, 2007, 80（2-3）：177-184．

[11]李瑞芳，高洁，乐康，等． 非诺贝特治疗大鼠左心室肥厚[J]. 中华高血压杂志, 2008, 16（5）：445-449．

备注/Memo

备注/Memo:

收稿日期：2010-02-20.基金项目：陕西省科学技术研究发展计划项目资助（2005K13-G1-3） 作者简介：赵晓燕，副主任医师，博士Email:zxysxy420@yahoo.com.cn

常用功能

更新日期/Last Update: 2010-10-27