三味甘露对大鼠肝纤维化的改善作用及机制

Ameliorative effect and mechanism of Sanwei ganlu on hepatic fibrosis in rats

目的探讨藏药三味甘露对大鼠肝纤维化的改善作用及机制。方法实验大鼠分为正常组、模型组、水飞蓟宾组(阳性对照,50mg/kg)和三味甘露低、中、高剂量组(80、250、800mg/kg),除正常组外,其余组以四氯化碳(CCl4)腹腔注射诱导大鼠肝纤维化模型。造模给药第6周开始,各组大鼠分别灌胃生理盐水或相应药物。第9周实验结束,计算大鼠肝脏指数和脾脏指数;以苏木素-伊红、Masson及SirusRed染色观察肝组织病理结构和纤维化程度;检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(COL-Ⅳ)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、IL-1β含量与肝组织中透明质酸(HA)、层粘连蛋白(LN)含量。结果与模型组相比,三味甘露各剂量组和水飞蓟宾组大鼠肝损伤和胶原纤维沉积均有不同程度改善,血清中ALT、AST、PCⅢ、COL-Ⅳ、IL-6、TNF-α、IL-1β含量以及肝组织中HA、LN含量均显著降低(P<0.05或P<0.01)。结论三味甘露能够通过抑制胶原纤维生成,降低转氨酶、HA、LN、PCⅢ和COL-Ⅳ含量,减轻炎症反应,从而缓解CCl4诱导的大鼠肝纤维化进程。

OBJECTIVE To investigate the ameliorative effects and mechanism of Sanwei ganlu on hepatic fibrosis in rats.METHODS The rats were randomly divided into normal group,model group,silibinin group(positive control,50 mg/kg),and Sanwei ganlu low-dose,medium-dose,and high-dose groups(80,250,800 mg/kg).Except for normal group,hepatic fibrosis rat models were established by intraperitoneal injection of CCl4 in the other groups of rats.Starting from the 6th week of modeling administration,they were given normal saline or corresponding drugs intragastrically at the same time.At the end of the ninth-week experiment,liver and spleen indexes of rats were calculated;the pathological structure and fibrosis changes of liver tissue were observed by HE,Masson and Sirus Red staining.The contents of alanine transaminase(ALT),aspartate transaminase(AST),procollagen typeⅢ(PCⅢ),collagen typeⅣ(COL-Ⅳ),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1βin serum,and hyaluronic acid(HA)and laminin(LN)in liver tissue were all detected.RESULTS Compared with the model group,the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group;the contents of ALT,AST,PCⅢ,COL-Ⅳ,IL-6,TNF-αand IL-1βin serum as well as the contents of HA and LN in liver tissue significantly decreased(P<0.05 or P<0.01).CONCLUSIONS Sanwei ganlu can alleviate the progression of hepatic fibrosis in rats,possibly by inhibiting the synthesis of collagen fiber,reducing transaminase content,down-regulating the levels of HA,LN,PCⅢand COL-Ⅳ,and reducing the inflammatory response.