miR-200s在中药丹芍化纤干预大鼠肝纤维化过程中的表达变化

Effects of traditional Chinese medicine Dan-shao-hua-xian capsule on expression of miR-200s in rat fibrotic livers

目的:观察肝组织中微小RNA-200家族成员(miR-200s)在肝纤维化形成及中药丹芍化纤胶囊干预过程中的表达变化并探讨其机制。方法:雄性Wistar大鼠皮下注射四氯化碳(CCl4)制备肝纤维化模型,干预组在给予CCl4造模同时给予丹芍化纤胶囊(0.5 g/kg)灌胃,分别在4周和8周处死大鼠,测定肝脏指数和血清谷丙/谷草转氨酶(ALT和AST)活性,观察肝组织病理改变,real-time PCR方法分别检测肝组织miR-200a、-200b、-200c、-141和-429表达变化。结果:模型组及干预4周组大鼠肝脏指数、血清ALT和AST活性显著高于正常对照组(P<0.01),8周模型组肝纤维化明显,并且肝组织中miR-200a、-200b、-200c、-141和-429表达较正常组显著增加(P<0.05)。丹芍化纤胶囊干预8周组肝功能生化指标及病理学改变与对照组无明显差异,且肝组织中miR-200a、-200b、-200c、-141和-429表达均低于8周模型组。结论:miR-200s在肝纤维化形成及中药丹芍化纤胶囊干预过程中的表达变化,提示其参与肝纤维化的发生发展并可能是潜在的中药作用靶点。

AIM： To investigate the effect of Dan-shao-hua-xian（DSHX） capsule on the expression of the family of microRNA-200（miR-200s） in rat fibrotic livers.METHODS： Forty male Wistar rats weighing 180 g to 220 g were divided into 5 groups（control group,two model groups and two interference groups）.The rats in model groups and interference groups were induced by hypodermic injection of CCl4 for 4 weeks and 8 weeks.The rats in interference groups were also treated with DSHX capsule（0.5 g/kg） once daily for 4 weeks and 8 weeks at the same time.The liver index and serum activity of ALT and AST were analyzed.The liver fibrosis was observed under microscope.Additionally,the expression of miR-200a,-200b,-200c,-141 and-429 was determined by quantitative real-time PCR.RESULTS： The liver index,and serum activity of ALT and AST in model groups and 4-week interference group were obviously higher than those in normal control group.The apparent liver fibrosis was observed in 8-week model group.The expression of miR-200a,-200b,-200c,-141 and-429 in the liver of 8-week model groups was obviously higher than that in control group.CONCLUSION： In the process of liver fibrosis induced by CCl4,the obvious changes of miR-200s may play an important role in the development of liver fibrosis.The miR-200s might be the potential target that DSHX capsule inhibits the process of liver fibrosis.