肝豆灵对铜负荷肝纤维化模型大鼠肝组织中转化生长因子β1、血小板源性生长因子表达的影响

Effects of Gandouling（肝豆灵） on the expression of TGF-β1 and PDGF in hepatic tissue of copper overload model rats with hepatic fibrosis

目的观察肝豆灵对铜负荷肝纤维化模型大鼠肝组织中转化生长因子β1(TGF-β1)、血小板源性生长因子(PDGF)表达的影响,探讨肝豆灵防治肝豆状核变性肝纤维化的作用机制。方法将60只Wistar大鼠采用随机数字表法分为空白组、模型组、青霉胺组、肝豆灵组4组,每组15只,通过喂食硫酸铜复制铜负荷大鼠模型,各组分别灌胃生理盐水及相应药物,采用免疫组化法检测各组大鼠肝组织中TGF-β1、PDGF的表达水平。结果与空白组比较,模型组大鼠肝组织中TGF-β1、PDGF的表达水平均明显升高,差异有统计学意义(P<0.01);与模型组比较,青霉胺组及肝豆灵组大鼠肝组织中TGF-β1、PDGF的表达水平均明显降低,差异有统计学意义(P<0.05或P<0.01)。结论肝豆灵可明显抑制铜负荷肝纤维化模型大鼠肝细胞p38丝裂素激活蛋白激酶信号通路下游因子TGF-β1、PDGF的表达,这可能是肝豆灵诱导肝星状细胞凋亡、防治肝豆状核变性肝纤维化的作用机制之一。

Objective To observe the effects of Gandouling(肝豆灵)on the expression of TGF-β1 and PDGF in hepatic tissue of copper overload model rats with hepatic fibrosis,and to discuss the mechanism of action of Gandouling in prevention and treatment of the hepatic fibrosis of Wilson’s disease(WD).Methods Sixty Wistar rats were divided into four groups according to random number table method,including blank group,model group,penicillamine group and Gandouling group,with 15 in each group.Copper sulfate was fed to replicate the copper overload model rats.Intragastric administration of normal saline and corresponding drugs to each group respectively.The expression levels of TGF-β1 and PDGF in hepatic tissue of the rats in each group was detected by immunohistochemical method.Results Compared with the blank group,the expression levels of TGF-β1 and PDGF in hepatic tissue of the rats in model group increased significantly,and the difference was statistically significant(P<0.01).Compared with the model group,the levels of TGF-β1 and PDGF in hepatic tissue of the rats in penicillamine group and Gandouling group decreased significantly,and the difference was statistically significant(P<0.05 or P<0.01).Conclusion Gandouling can markedly inhibit the expression of downstream factors TGF-β1 and PDGF of p38 mitogen-activated protein kinase(MAPK)signaling pathway in hepatocytes of copper overload model rats with hepatic fibrosis,which maybe one of the mechanism of action of Gandouling in inducing the apoptosis of hepatic stellate cells and prevention and treatment of hepatic fibrosis of WD.