摘要
目的:通过观察转化生长因子-β1(transforming growth factor-β1,TGF-β1)、β-连环蛋白(β-catenin)mRNA和蛋白质的表达,探讨清热祛湿活血法干预大鼠肝纤维化的分子机制.方法:成年♂Wistar大鼠60只随机分组为给药组(中药和秋水仙碱)、造模组和正常组。造模组给予四氯化碳皮下注射,辅以高脂饮食和30 mL/L乙醇为唯一饮用水,共16 wk.第5周起给予中药和秋水仙碱组每天灌胃干预,12 wk后处死,检测各组大鼠血清透明质酸酶(hyaluronidase,HA)、Ⅳ胶原蛋白、Ⅲ型前胶原(procollagen typeⅢ,PCⅢ)、层黏连蛋白(laminin,LN)血清水平,HE染色和Masson染色观察各组大鼠肝组织病理变化情况,RTPCR和Western blot检测TGF-β1和β-catenin mRNA和蛋白质表达水平.结果:中药组大鼠HE染色及Masson染色均见中药组大鼠肝纤维化程度较造模组和秋水仙碱组减轻,血清Ⅳ型胶原蛋白、HA、Ⅲ型前胶原氨基末端肽(N-terminal procollagenⅢpropeptide,PⅢNP)值均明显下降.中药组大鼠肝脏组织内TGF-β1、β-catenin在mRNA和蛋白质表达水平上均低于造模组大鼠和秋水仙碱组大鼠.结论:基于清热祛湿活血立法的加味茵芍散对大鼠肝纤维化有一定的逆转作用,其抗肝纤维化分子机制可能与抑制或下调TGF-β1、β-catenin mRNA和蛋白质的表达,从而阻断TGF-β1、Wnt/β-catenin细胞通路的激活有关.
AIM：To investigate the effect of traditional Chinese medicine Yinshao powder on the expression of transforming growth factor-β1（TGF-β1） and p-catenin in hepatic fibrosis in rats to clarify the molecular mechanism of clearing heat,expelling damp and promoting blood circulation.METHODS：Sixty adult male Wistar rats were divided randomly into six groups：a normal control group,a model group,low-,mediumand high-dose Yinshao powder groups and a colchicine group.Hepatic fibrosis was induced by giving subcutaneous injection of carbon tetrachloride,a high-fat diet and 30 mL/L alcohol for 16 wk.At the fifth week,Yinshao powder or colchicine was intragastrically administered.After 12 wk of treatment,the rats were sacrificed to measure serum levels of hyaluronidase（HA）,type IV collagen,procollagen type Ⅲ（PCⅢ）,and laminin（LN）,observe hepatic pathological changes by HE staining and Masson staining,and determine the mRNA and protein expression levels of TGF-pi and p-catenin by RT-PCR and Western blot.RESULTS：Compared with the colchicine group and model group,serum levels of HA,type IV collagen,PCIII,and LN declined significantly in the other groups.The degree of hepatic fibrosis in the Yinshao powder groups was less than that in the colchicine group and model group.The mRNA and protein expression levels of TGF-pi and p-catenin were significantly lower in the Yinshao powder groups than in the model group and colchicine group.CONCLUSION：Clearing heat,expelling damp and promoting blood circulation with Yinshao powder for intervention of hepatic fibrosis may be via molecular mechanisms associated with inhibiting or down-regulating the expression of TGF-β1 and p-catenin and blocking the activation of TGF-pi signaling pathway and Wnt/β-catenin signaling pathway.
出处
《世界华人消化杂志》
CAS
2015年第17期2697-2706,共10页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.81173180
福建省自然科学基金资助项目
No.2011J01216~~
