壮医方白花丹消蛊汤对食蟹猴肝纤维化的干预作用及机制

Effect and Mechanism of Zhuang Medicine Baihuadan Xiaogu Decoction on Treating Experimental Liver Fibrosis in Macaca Fascicularis

目的研究壮医方白花丹消蛊汤对食蟹猴肝纤维化的干预作用及其机制。方法将食蟹猴随机分为4组,除空白对照组外,其余各组每周2次皮下注射60%四氯化碳(CCI4)油剂0.5 m L·kg^(-1),同时辅以高脂饲料喂养,建立食蟹猴肝纤维化模型。造模6个月后,各组相应给药,白花丹消蛊汤小、大剂量组分别灌胃给予1.0,4.0 g·kg^(-1)(按处方生药量计算)汤药,空白对照组和模型对照组给予等体积纯化水。给药2个月后,静脉采集食蟹猴血液样本,检测各组食蟹猴血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(T-BiL)含量,酶联免疫吸附测定法(ELISA)检测食蟹猴血清中转化生长因子-β(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、血清基质金属蛋白酶2(MMP-2)、基质金属蛋白酶抑制剂-1(TIMP-1)水平,免疫组化观察肝组织TGF-β1的表达情况。结果与模型对照组比较,白花丹消蛊汤能降低肝纤维化食蟹猴血清ALT、AST、T-BiL含量,能降低其血清中α-SMA及相关基质金属蛋白酶水平,能调控肝纤维化食蟹猴肝组织TGF-β1的升高。结论壮医方白花丹消蛊汤具有抗肝纤维化作用,降低TGF-β1、α-SMA表达、调节肝脏细胞外基质的代谢是其发挥抗肝纤维化作用的部分机制。

Objective To investigate the effect and mechanism of Baihuadan Xiaogu decoction(BHD)in liver fibrosis.Methods Macaca fascicularis were divided into four groups:the normal control group,the model control group,the BHD-L group and BHD-H group.Hepatic fibrosis models establish by CCl 4(0.5 mL·kg-1)twice a week for 6 month,at the same time,high fat diet was feed.After six months,BHD-L and BHD-H(1.0,4.0 g·kg-1)were administered orally to groups respectively,whereas the normal control and model control groups were orally administered with pure water.Two months later,the blood sample was collected for the examination of alanine aminotransferase(ALT),glutamic oxalacetic transaminase(AST),and total bilirubin(T-BiL).The contents of transforming growth factor-β(TGF-β),alpha-smooth muscle actin(α-SMA),matrix metalloprotein(MMP-2)and tissue inhibitor of metalloproteinase-1(TIMP-1)in serum were analyzed by ELISA assay.The expression of TGF-β1 in liver biopsy specimens was detected by immunohistochemical staining.Results Compared with model control group,both BHD groups can reduce the levels of Macaca fascicularis serum ALT,AST,T-BiL.It can reduce the levels of TGF-β1,α-SMA and related matrix metalloprotein,regulatory effects on the expression of TGF-β1.Conclusion BHD can prevent liver fibrosis in Macaca fascicularis by reducing the level of TGF-β1,α-SMA and regulate the liver extracellular matrix metabolism.