中国组织工程研究Issue(20)：3715-3722,8.DOI:10.3969/j.issn.2095-4344.2013.20.015
丹参酮ⅡA抑制心肌细胞的纤维化**
Tanshinone ⅡA inhibits cardiac fibrosis
摘要
Abstract
BACKGROUND: Transforming growth factor β-Smads is the critical path of cardiac fibrosis, and tanshinone ⅡA can limit cardiac fibrosis. OBJECTIVE: To explore the effect of tanshinone ⅡA on the cardiac fibrosis induced by transforming growth factor-β1 and the possible mechanisms. METHODS: Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley rats by the trypsin digestion and differential adhesion method. Passage 3 cel s were treated with 5 μg/L transforming growth factor β1 alone or pretreated with tanshinone ⅡA at different concentrations (10-5 mol/L and 10-4 RESULTS AND CONCLUSION: Transforming growth factor-β1 induced the expression of connective tissue growth factor, type Ⅰ col agen, phosphorylated Smads and Smad7 in a time-dependant manner. The mRNA expression of connective tissue growth factor and type Ⅰ col agen was significantly increased 24 hours after transforming growth factor-β1 stimulation (P < 0.01 for al ). The protein expression of phosphorylated Smad3 and Smad7 reached a peak 1 hour after transforming growth factor-β1 stimulation, much higher than the baseline level (P < 0.01 for al ). Pretreatment with high concentration of tanshinone ⅡA resulted in a decrease in the expression of phosphorylated Smad3, connective tissue growth factor and type Ⅰ col agen (P < 0.01). The protein expression of Smad7 was substantial y upregulated after pretreatment with two concentrations of tanshinone ⅡA as compared with that in the cel s at 2 hours post transforming growth factor-β1 stimulation (P < 0.05, P < 0.01). Tanshinone ⅡA may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the transforming growth factor-β1-induced phosphorylated Smad3 and partial y blocking the transforming growth factor-β1-Smads signaling pathway. mol/L). Immunocytochemistry was used for cel identification, reverse transcription-PCR for detection of the mRNA expression of connective tissue growth factor and type Ⅰ col agen, western blotting for detection of the protein expression of Smad7 and phosphorylated Smad3, and immunohistochemistry and immunofluorescence for detection of the protein expression of phosphorylated Smad3, connective tissue growth factor and type Ⅰ col agen.关键词
组织构建/组织构建与中医药/丹参酮ⅡA/心肌成纤维细胞/心肌纤维化/转化生长因子β1/Smad3/Smad7/结缔组织生长因子/Ⅰ型胶原/信号通路/细胞培养/省级基金分类
医药卫生引用本文复制引用
周代星,李智慧,占成业,张莉伟..丹参酮ⅡA抑制心肌细胞的纤维化**[J].中国组织工程研究,2013,(20):3715-3722,8.基金项目
湖北省自然科学基金资助项目(2009CDB092,2007ABA272)。 （2009CDB092,2007ABA272）
