重组人IL-22对大鼠酒精性肝炎的治疗效果评价

Therapeutic evaluation of recombinant human interleukin-22 on alcoholic hepatitis in rats

目的建立一种稳定的大鼠酒精性肝炎模型,并利用该模型对IL-22的治疗效果进行评价。方法雄性Wistar大鼠60只,随机分为对照组10只,模型组50只,利用酒精、高脂饲料以及碳酰铁联合诱导建立酒精性肝炎模型,分别在第16周,24周,32周时检测血清转氨酶及组织病理学变化。在确定出现酒精性肝炎病理变化后,将模型组大鼠随机分为模型对照组(10只)以及IL-22治疗组(10只),IL-22治疗组尾静脉注射重组hIL-22蛋白(0.5 mg/kg),隔天给药,共注射10次,实验结束后处死大鼠,测定各组血清甘油三酯(TG),总胆固醇(CHO),丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST)以及γ-谷氨酰氨基转移酶(GGT)水平,并进行组织病理学检查。结果随着造模时间的增加,血清转氨酶呈进行性升高,且差异具有统计学意义(P<0.05),肝脏组织病理学由小泡状肝脂变逐渐进展为大泡状肝脂变伴有炎性细胞的浸润以及Mallory小体的形成,表现为典型的酒精性肝炎病理学改变。IL-22治疗可以降低血清转氨酶,总胆固醇以及甘油三酯水平,在一定程度上改善组织病理学变化。结论酒精、高脂饲料以及碳酰铁联合应用可以诱导大鼠酒精性肝炎模型,IL-22治疗可明显改善酒精性肝炎的血清学及病理学变化,提示IL-22可以作为酒精性肝炎治疗的候选药物。

Objective To construct a reliable rat animal model with alcoholic hepatitis and investigate the effect of IL- 22 on such model. Methods Sixty male Wistar rats were randomly divided into two groups ： normal control group and alco- hol group. The combination of alcohol, high fat diet as well as carbonyl iron was used to induce alcoholic hepatitis in rats. The level of serum aminotransferases and hepatic histopathology were examined at 16, 24 and 32 weeks respectively. When histopathological changes of alcoholic hepatitis occurred, IL-22 was given by the tail vein at the dose of O. 5 mg/kg for a to- tal of 10 times. At the end of the experiment, the changes of serum ALT, AST, GGT, TG and CHO as well as hepatic pa- thology in different groups were detected respectively. Results At 32 weeks, histopathologieal changes of alcoholic hepati- tis occurred and the serum ALT, AST, GGT, TG and CHO were significantly elevated. Treatment with IL-22 could reverse the above adverse changes. Conclusion The joint use of alcohol, high fat diet and carbonyl iron can induce a reliable rat animal model with alcoholic hepatitis. IL-22 can significantly decrease the elevation of serum enzymes and improve histopa- thology of alcoholic hepatitis in the rat model ,suggesting that IL-22 is a potential drug for alcoholic hepatitis.