AIM: To investigate the effect of rhein on liver fibrosis induced by the exposure of carbon tetrachloride (CC14)/ethanol in rats. METHODS: Male Wistar rats were divided into four study groups (n=10 each group): healthy controls, CCl4/ethanol-injured rats left untreated, and CCldethanol-injured rats treated with rhein of low-dose (25 mg.kg-1) and high-dose (100 mg@kg-1). Rhein was given once a day since rat received CCl4/ethanol injury. After administration of rhein for 6 weeks rats were killed. The following parameters were determined: the activity of alanine aminotransferase (ALT), hyalauronic acid (HA) and procollagen type III (PC-III) concentrations in serum,liver malondialdehyde (MDA) level, the degree of liver fibrosis, and the expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in liver tissue. RESULTS: The treatment of rhein markedly reduced the ALT activity, HA and PC-III concentrations, and liver MDA level in CCl4/ethanol-injured rats (P＜0.01).It also improved significantly histological changes of fibrosis and decreased the expression of α-SMA and TGF-β1 in liver of these rats (P＜0.05 or P＜0.01). CONCLUSION: Rhein has protective effect on liver injury and can inhibit liver fibrosis induced by CCl4/ethanol in rats. The mechanisms possibly contribute to its action of antioxidant and anti-inflammatory activity, also associated with its effect of inhibiting TGF-β1 and suppressing the activation of hepatic stellate cells.%目的:观察大黄酸对实验性肝纤维化的影响.方法:采用60%的四氯化碳(CCl4)及5%的乙醇制备肝纤维化动物模型,分别用小剂量、大剂量大黄酸(25 mg/kg,100 mg/kg体重)干预,测定血清丙氨酸氨基转移酶(ALT)、透明质酸(HA)、III型前胶(PC-III)及肝组织丙二醛(MDA)含量,免疫组化方法观察转化生长因子p1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)的表达情况,并观察肝组织胶原面积及病理变化.结果:大黄酸组较模型组:(1)血清ALT、HA、PC-III水平及肝组织中MDA含量显著降低(P＜0.01);(2)肝组织中TGF-β1,α-SMA的表达显著减少(P＜0.05或P＜0.01);(3)肝组织胶原面积明显减少,纤维化程度明显改善(P＜0.0 5或P＜0.01).结论:大黄酸具有保肝作用和抑制肝纤维化作用,其作用机制可能与其抗炎、抗氧化作用及抑制HSC活化、抑制TGF-β1作用有关.
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