Effect Of Tetrandrine On Experimental Hepatic Fibrosis Induced By Thioacetamide And Bile Duct Ligation In Rats

Objective: To investigate the apoptosis of hepatic stellate cells induced by:etrandrine and examine the effects of the tetrandrine for liver fibrosis induced by the :hioacetamide and bile duct ligation in rats.Methods: In vitro study, we investigated the apoptosis on rat hepatic stellate cells. In vivo study, hepatic fibrosis was induced in rats by thioacetamide and bile duct ligation. The tetrandrine was administrated orally to rats at doses of 5, 10, 20 mg/kg throughout 28days compared with intraperitoneally injection of interferon-r, and the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST) , total bilirubin (T-Bil), liver hydroxyproline (liver Hyp), Hyaluronic Acid (HA) and Laminin (LN) in serum were determined, and then histopathological changeswas observed. Results: In vitro study. T-HSC/C1-6 cells were exposed to 0.5-2.5 uMtetrandrine caused a dose-dependent reduction on cell viability. The characteristic apoptotic DNA ladder was observed at 5 uM tetrandrine and increased as dose-dependent manner. In vivo study, tetrandrine treatment as well as interferon-r significantly ameliorates development of fibrosis as determined by lower serum levels of AST, ALT, T-Bil, and the levels of Hyp, HA and LN, in accordance w ith improved histopathological findings. The effects of tetrandrine at 20mg/kg dose are better than the other groups but there is no statistical significance..Conclusion: The tetrandrine could promotes the apoptosis of HSCs in vitro at concentrations, and the tetrandrine administration could improve liver fibrosis and injury induced by thioacetamide and bile duct ligation in rats in vivo, indicating that it might exert a direct effects for HSCs of rats.