干扰素α预防实验大鼠肝纤维化的作用机制

The suppressive effects of interferon-alpha on experimental hepatic fibrosis induced by CCl_4 in rats

目的 探讨干扰素α(IFNα)预防肝纤维化的作用机制。方法 雄性SD大鼠 36只随机分成A组 (对照组 ) 12只 ,正常饮水 ,皮下注射花生油 ;B组 (模型组 ) 12只 ,复合因素制成肝纤维化模型 ;C组 (IFNα预防组 ) 12只 ,造模方法同B组 ,干扰素α 1× 10 5U肌注 ,1次·d-1。 6周后处死观察肝内纤维组织、肝星状细胞 (HSC)、α 平滑肌动蛋白 (α SMA)及肝功能变化。结果 与B组相比 ,C组肝内Ⅰ、Ⅲ型胶原、血清Ⅲ型前胶原 (PCⅢ )、透明质酸 (HA)及层黏蛋白 (LN)明显降低 (P <0 .0 1) ,活化的HSC数目减少 ,凋亡数目增多 ,肝功损伤减轻。结论 IFNα通过减轻肝组织炎症和抑制HSC活化、诱导其凋亡预防肝纤维化。

Objective To investigate the mechanism of inter fe ron-α (IFNα) in preventing hepatic fibrosis in rat experimental model . Methods Thirty-six male Sprague-Dawley rats were divide d into three groups randomly: group A(normal controls)of 12 rats were given norm al food and water and received subcutaneous injection of peanut oil twice weekly ; group B (fibrotic model)and group C (IFNα prevention) with 12 rats in eac h were induced by carbon terrachloride, high cholesterol and low protein. Group C were treated with intramusclular injections of IFNα in saline, administered daily at the doses of 1×10 5U. At the end of the sixth week, all the rats in each group were killed, the liver function was examined and the samples of t he liver obtained by biopsy were submitted to histological liver fibrosis studie s. The expressions of α-smooth muscle actin in hepatic tissues were detect ed with immunohistochemical methods. The effect of IFNα on apoptosis of hep atic stellate cells (HSC) were investigated under electron microscope. Results The level of hepatic collagen Ⅰand Ⅲ and serum PC Ⅲ, HA, and LN in group C was significantly lower than that of group B under lig ht microscope (P<0.01). After IFNα prevention, the number of activated HSC decreased and the apoptosis of HSC could be seen upon liver histological exa mination. The activities of serum ALT and AST in group C were lower than those o f group B. Conclusion IFNα can inhibit HSC proliferat ion and stimulate its apoptosis, which may partly account for the suppressive ef fect of IFNα on liver fibrosis.