IFN-γ受体Ig融合蛋白对ConA诱导小鼠肝损伤的保护作用  

Preventive Effect of IFN-γ Receptor-Immunoglobulin Fusion Protein on Liver Demages Induced by ConA in Mice

作　　者：向明[1] 孙汉清[1] 裘军[1] 张进芳[1] 郝长江[1] 

机构地区：[1]华中科技大学同济医学院药学系药理教研室,武汉430030

出　　处：《上海免疫学杂志》2001年第6期337-339,共3页Shanghai Journal of Immunology

基　　金：湖北省自然科学基金资助项目 ( 2 0 0 0J0 39)

摘　　要：本文研究γ 干扰素受体免疫球蛋白融合蛋白 (IFN γR Ig )对ConA诱导的小鼠细胞免疫性肝损伤的保护作用及机制。在Balb/c小鼠体内一次性静脉注射ConA 2 0mg/kg诱导细胞免疫性肝损伤模型 ,分别于模型建立前后不同时间腹腔注射 10mg/kgIFN γR Ig,观察该融合蛋白对小鼠血清谷丙转氨酶 (GPT )水平 ,细胞因子IFN γ、TNF α和IL 10分泌以及肝组织病理学变化的影响。结果表明IFN γR Ig预防给药明显改善肝脏损伤的组织学和血清学变化 ,降低GPT水平 ,减少肝脏中性粒细胞、单核细胞浸润 ;同时与模型对照小鼠相比血清IFN γ水平下降 ,TNF α分泌合成减少 ,IL 10水平明显增加。而IFN γR Ig通过早期结合并阻断内源性IFN γ ,提高IL 10的抗炎作用 ,减轻炎症细胞对肝脏的侵袭及IFN γ、TNF α的肝细胞破坏作用 ,保护免疫性肝损伤。To investigate the preventive effect and mechanism of mouse IFN-γR-Immunoglubulin fusion protein(IFN-γR-Ig) on the T cell dependent liver demages induced by ConA,the mouse model was established by intravenous injection of 20 mg/kg ConA and 10 mg/kg of IFN-γR-Ig were prophylactically and therapeutically administrated once respectively,and then the serum levels of IFN-γ,TNF-α and IL-10 and the activity of transaminase were determined together with the detection of histopathologic changes. Experimental results showed that pretreatment with IFN-γR-Ig significantly decreased the serum level of GPT and could minimize the liver demages by reducing the hepatic infiltrations of mononuclear cells,lymphocytes and neutrophils. In addition,serum levels of IFN-γ and TNF-α were significantly lower and the secretion of IL-10 were significantly higher than those in the controls. It concludes that IFN-γR-Ig may protect the immune hepatic injuries by directly blocking endogenous secretion of IFN-γ and indirectly suppressing the production of TNF-α,as well as increasing the synthesis of IL-10.

关 键 词：IFN-Γ R-Ig 肝损伤 细胞因子 Γ-干扰素 融合蛋白 自身免疫性疾病 

分 类 号：R979.5[医药卫生—药品] R593.2[医药卫生—药学]