中国组织工程研究与临床康复2010，Vol.14Issue(37)：7021-7025,5.DOI:10.3969/j.issn.1673-8225.2010.37.043
丹参酮ⅡA对心脏成纤维细胞转化生长因子β1/Smads信号通路的作用
Effects of tanshinone ⅡA on transforming growth factor beta 1/Smads signaling pathway in cardiac fibroblasts
摘要
Abstract
BACKGROUND: One of important mechanisms underlying myocardial fibrosis is that transforming growth factor β1(TGF-β1) stimulates the proliferation and differentiation of cardiac fibroblasts via Smads signaling pathway.Previous studies have confirmed that tanshinone ⅡA can effectively inhibit myocardial fibrosis.But whether blockage of TGF-β1/Smads signaling pathway is involved in this process remains unclear. OBJECTIVE: To investigate the effects of tanshinone ⅡA on TGF-β1 signal transduction in rat cardiac fibroblasts. METHODS: Neonatal rat cardiac fibroblasts were harvested by trypsin digestion and differential attachment and treated with 5 μg/L TGF-βI and different concentrations of tanshinone Ⅱ A(106,10-5 and 10-4 mol/L).At 6,12,and 24 hours after TGF-β1 application,fibronectin expression was detected by reverse transcription-polymerase chain reaction and Western blot analysis.At 15,30,60,and 120 minutes after TGF-β1 application,Smads protein expression was determined by Western blot analysis. RESULTS AND CONCLUSION: Fibronectin mRNA and protein expression began to increase at 6 hours after TGF-β1 application and was 1.3 and 1.8 times higher than initial level,respectively(P < 0.01),at 24 hours after TGF-β1 application.Phosphorylated Smad2/3 protein expression began to increase at 15 minutes after TGF-β1 application,peaked at 1 hour,decreased at 2 hours,but it was still 3.9 times higher than initial level(P < 0.01).Tanshinone ⅡA(10-5 and 10-4 mol/L)pretreatment downregulated fibronectin and phosphorylated Smad2/3 expression(P < 0.05 or P < 0.01)in a dose-dependent manner.These findings demonstrate that TGF-β1 induced fibronectin protein and mRNA expression and Smad2/3 protein expression in a time-dependent manner.Tanshinone ⅡA against myocardial fibrosis was likely related to its inhibition of TGF-β1-induced Smad2/3 phosphorylation and blockage of TGF-β1/Smads signaling pathways within cardiac fibroblasts.关键词
丹参酮ⅡA/成纤维细胞/转化生长因子β1/Smads/组织构建分类
医药卫生引用本文复制引用
占成业,周代星,唐锦辉..丹参酮ⅡA对心脏成纤维细胞转化生长因子β1/Smads信号通路的作用[J].中国组织工程研究与临床康复,2010,14(37):7021-7025,5.基金项目
本课题为湖北省自然科学基金(2007ABA272,2009CDB092)资助. （2007ABA272,2009CDB092）
