丹参酮ⅡA干预肝纤维化模型大鼠相关信号通路相关因子的表达

摘要

BACKGROUND:Liver fibrosis is a kind of chronic and active disease that is caused by various causes and characterized by the excessive accumulation of extracelular matrix. At present, use of Chinese herbs for the treatment of hepatic fibrosis has obvious advantages. Salvia miltiorrhiza has been shown to be highly effective in the treatment of hepatic fibrosis. However, the underlying mechanism needs further investigation. OBJECTIVE:To investigate the effects of TanshinoneⅡA on the expression levels of transforming growth factor-β/Smads signaling pathway related factors transforming growth factor-β, bone morphogenetic protein 7, Smad6 and Smad7 in the liver tissue of rats with hepatic fibrosis. METHODS:SD rats were randomly divided into three groups (n = 10): normal control, model and TanshinoneⅡA-treated groups. Rats in the model and TanshinoneⅡA-treated groups were subtaneously injected with olive oil-diluted 10% CCl4 ( 5 mL/kg) twice a week, 8 weeks in total, to build rat models of hepatic fibrosis. Four weeks after hepatic fibgrosis induction, rats in the TanshinoneⅡA-treated group received subtaneous injection of TanshinoneⅡA til eight weeks. Rats in the normal control group were subcutaneously injected with olive oil. RESULTS AND CONCLUSION: Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) detection showed that in the model group, the expression of transforming growth factor-β in the rat liver tissue was significantly increased (P < 0.01) and the expression of bone morphogenetic protein-7, Smad6 and Smad7 was significantly decreased (P < 0.01) compared with the normal control group. TanshinoneⅡA could obviously reverse the expression of those factors above-mentioned (P < 0.01). The results suggest that TanshinoneⅡA can be used for treatment of hepatic fibrosis by decreasing the expression of transforming growth factor-β and increasing the expression of bone morphogenetic protein-7, Smad6 and Smad7.%背景：肝纤维化是一种由多种病因导致的以细胞外基质过度沉积为特点的慢性活动性疾病，目前中药治疗肝纤维化具有显著优势。研究表明丹参治疗肝纤维化具有较好的疗效，但其作用机制尚需进一步研究。目的：研究丹参酮ⅡA对肝纤维化大鼠肝脏转化生长因子β-Smads信号通路相关因子转化生长因子β，骨形态发生蛋白7及Smad6，7基因表达的影响。方法：随机将SD大鼠分为正常对照组、模型组和丹参酮ⅡA治疗组，模型组和丹参酮ⅡA治疗组给予橄榄油稀释的体积分数10%四氯化碳5 mL/kg皮下注射，每周2次，共8周，建立肝纤维化模型。建模后第4周，丹参酮ⅡA治疗组给予丹参酮ⅡA治疗至第8周。正常对照组以同样方法皮下注射橄榄油。结果与结论：Western印迹检测和RT-PCR检测显示，与正常对照组相比，模型组大鼠肝组织转化生长因子β的表达明显增加(P <0.01)，而其抑制因子骨形态发生蛋白7和Smad6，7的表达明显减少(P <0.01)，丹参酮ⅡA可明显逆转上述因子的表达(P <0.01)。结果提示，丹参酮ⅡA治疗肝纤维化可能与其抑制转化生长因子β，增加其抑制因子骨形态发生蛋白7和Smad6，7的表达有关。