Preliminary Study on Improvement Effect of Tiarella polyphylla Ethanol Extract on CCl 4-induced Hepatic Fibrosis in Mice and Its Mechanism / 中国药房

ABSTRACT

OBJECTIVE：To investigate the improvement effect of Tiarella polyphylla ethanol extract （TPME）on CCl 4-induced hepatic fibrosis in mice ，and to explore its possible mechanism preliminarily. METHODS ：Totally 60 male Kunming mice were randomly divided into normal group ，model group ，positive control group （colchicine 0.1 mg/kg），TPME low-dose ，medium-dose and high-dose groups （250，500，1 000 mg/kg）according to body weight ，with 10 mice in each group. Except for normal group ， other groups were given 20％ CCl4 olive oil solution intraperitoneally to induce hepatic fibrosis ，twice a week ，for consecutive 8 weeks. From the fifth week after modeling ，administration groups were given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. Twelve hours after last administration ，the liver weight of mice in each group was measured and the liver index was calculated. The serum contents of ALT，AST，SOD，MDA，PC-Ⅲ，C-Ⅳ，LN，TNF-α and IL- 6 were determined. Western blot assay was used to detect the protein expression of α-SMA，TGF-β1 and Smad 3 in liver tissue. HE and Masson staining were used to observe the pathological changes of hepatic tissue. RESULTS ：Compared with normal group ，the liver index ，the activities of ALT and AST and the contents of MDA ， LN，PC- Ⅲ ，C- Ⅳ ，LN，TNF-α and IL- 6 in serum were increased significantly ， while the activity of SOD was 6011） decreased significantly in model group （P＜0.01）；the protein expression of α-SMA，TGF-β1 and Smad 3 in liver tissues were hfjsznd8@126.com increased significantly （P＜0.01）. Obvious fibrosis lesions was observed in liver tissue. Compared with model group ，the live indexes ，the activities of ALT and AST ，the contents of MDA，PC-Ⅲ，C-Ⅳ，LN，TNF-α and IL-6 in serum were decreased significantly in positive control group and TPME groups ， while the activities of SOD were increased significantly （P＜0.05 or P＜0.01）. The protein expression of α-SMA，TGF-β1 and Smad3 in liver tissue were decreased significantly （P＜0.05 or P＜0.01），and liver fibrosis was improved to different extent. Compared with TPME low-dose group ，the contents of PC- Ⅲ，LN and IL- 6 in serum ，protein expression of TGF-β1 and Smad 3 in liver tissue were decreased significantly in TPME high-dose group （P＜0.05）. CONCLUSIONS ：TPME can improve hepatic fibrosis induced by CCl 4 in mice ，the mechanism of which may be associated with the inhibition of collagen synthesis and oxidative stress，the reduction of inflammatory factors ，and the down-regulation of the expression α-SMA and relative proteins of TGF-β1/ Smad signal pathway.