不同剂量γ-干扰素治疗大鼠肝纤维化疗效研究  

Recombinant human gamma-Interferon decreases liver collagen accumulation in two kinds of rat fibrosis model

作　　者：翁红雷[1] 蔡卫民[1] 汪国运 刘荣华[1] 

机构地区：[1]浙江大学医学院附属第一医院传染病研究所,杭州310003 [2]解放军第475医院

出　　处：《中华传染病杂志》2001年第5期285-288,T006,共5页Chinese Journal of Infectious Diseases

摘　　要：目的　观察不同剂量重组人γ 干扰素 (IFN γ)对不同原因引起的大鼠肝纤维化的治疗效果。方法　用四氯化碳 (CCl4 )和二甲基亚硝胺 (DMN)分别诱导形成大鼠肝纤维化模型 ,采用 3种不同剂量IFN γ对 2种模型肝纤维化大鼠进行治疗 ,并与正常对照组、秋水仙碱治疗组和模型对照组相比较 ,观察各组肝功能、血清透明质酸 (HA)水平、肝组织羟脯氨酸 (Hyp)含量、病理组织学、免疫组化α SMA的变化。结果　 2种模型组中 ,3组IFN γ治疗组肝纤维化程度均明显小于秋水仙碱治疗组和模型对照组 ,部分肝功能指标、肝Hyp含量、血清HA水平较秋水仙碱治疗组和模型对照组亦有显著降低。 3组IFN γ治疗组之间 ,随剂量增大存在明显量效关系。结论　IFN γ对不同原因引起的大鼠肝纤维化有较好疗效 ,IFNObjective To evaluate the antifibrotic effect of different doses of recombinant Gamma Interferon(IFN γ) in two kinds of rat fibrosis model Methods Liver fibrosis was successfully induced in 150 rats by subcutaneous injection of carbon tetrachloride(CCl 4) and in 196 rats by intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into 1) Fibrotic model group,2) Colchicine treatment group, 0.1 mg/kg/day, gastrogavage for 8 weeks,3) High dose IFN γ group(15 MU/kg/day, i.m. for 8 weeks),4) Medium dose IFN γ group(5 MU/kg/day, i.m. for 8 weeks),5) Low dose IFN γ group (1.67 MU/kg/day, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal control. At the end of the experiment, semi quntitative histopathological scores of inflammation and fibrosis, levels of liver α smooth musule actin(α SMA) expression, liver hydroxyl proline and serum hyaluronic acid were compared. Results Compared with those in fibrotic models induced by either CCl 4 or DMN, the histopathological fibrosis scores, liver hydroxyl proline content and serum hyaluronic acid levels were significantly lower in rats treated with colchicine or different doses of IFN γ, in a dose dependent manner( P <0.05). Conclusion All of the three doses of IFN γ are effective in treating rat liver fibrosis induced by either CCl 4 or DMN, the higher the dose, the better the efficacy.

关 键 词：肝纤维化 Γ-干扰素 四氯化碳 二甲基亚硝胺 大鼠 

分 类 号：R575.2[医药卫生—消化系统]