关键词: 吡非尼酮, 四氯化碳, 肝纤维化, 肝星状细胞, 小鼠

Abstract: Objective:To investigate the effects of pirfenidone on CCl4-induced liver fibrosis in mice. Methods:After 8-week feeding, 40 healthy male SPF ICR mice were randomly divided into 4 groups:liver fibrosis group (CCL₄ group), low doses of Pirfenidone group (PFD-L group), high doses of Pirfenidone group (PFD-H group) and control group. The mice in CCL₄ group, low doses of Pirfenidone group (PFD-L group), high doses of Pirfenidone group (PFD-H group) were injected intraperitoneally with 0.4 ml 10% CCL₄ solution dissolved in soybean oil. Then the PFD-L and PFD-H groups were treated with 120 mg and 240 mg PFD via gastric gavage, respectively. Control group was injected with same volume of saline. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum were tested with automatic biochemistry analyzer and the pathologic changes of liver tissue were examined by HE staining. Furthermore, we identi-fied hyaluronic acids(HA), laminin(LN), collagentype IV(IV-C) in serum using radioimmunoassay and the expression of smooth muscle acti-nalpha(α-SMA) related gene in liver was tested by real-time fluorescence quantitative PCR. Results:Compared with control group, hepatic lobules in CCL₄ mice were damaged significantly, collagenous fiber was deposited obviously, and counterfeit hepatic lobules formed. The serum levels of ALT, AST, ALP were increased obviously (P<0.05) with the enhancement of HA, LN, IV-C in serum (P<0.05) and the ex-pression of α-SMA related gene (P<0.05). Compared to CCL₄-treated mice, the serum levels of ALT, AST, ALP in PFD-L and PFD-H groups were decreased, HA, LN, IV-C in PFD-L and PFD-H mice went down obviously,and the expression of α-SMA related gene was con-trolled (P<0.05). From pathological observation, we found the degree of liver fibrosis in PFD-L mice was reduced and collagenous fiber was decreased, only a little counterfeit hepatic lobule could be found. Cell arrangement in PFD-H mice recovered, the structural of hepatic lobules disordered and no obvious counterfeit hepatic lobules were found. Therefore, the recovery of PFD-H group was better than PFD-L group.Conclusion:Pirfenidone has a protective role in improving the outcome of the liver fibrosis and it may become a new direction of early intervention in liver fibrosis.

Key words: pirfenidone, carbon tetrachloride, hepatic fibrosis, hepatic stellate cells, mice