IL-10对大鼠肝纤维化的治疗作用及对TNF-α、IGF-1及IGF-1R表达的影响

The therapeutic effect of IL-10 and effects of IL-10 on expression of TNF-α、IGF-1 and IGF-1R in fibrotic rat liver

目的外源性白介素10(IL10)对大鼠肝纤维化的治疗作用及对肿瘤坏死因子α(TNFα)和胰岛素样生长因子1(IGF1)及其受体(IGF1R)表达的影响。方法40只SD大鼠随机分为正常对照组和CCl4诱发肝纤维化模型组。至造模第9周,模型组随机分为3组,S组造模结束即处死,I组IL10治疗2周后处死,R组为自然恢复2周后处死。通过HE染色评价各组肝纤维化的程度,SP免疫组化检测各组大鼠肝脏TNFα、IGF1、IGF1R表达情况。结果肝病理组织学显示:I组纤维化程度有明显改善,R组纤维化程度没有明显改善。TNFα、IGF1、IGF1R在S组表达显著升高(P<0.05),在R组及I组表达下降,但I组下降较R组明显,与R组比较差别有显著意义(P<0.05)。结论外源性IL10能明显抑制炎性细胞因子TNFα的表达和IGF1及IGF1R的表达,这可能是IL10对大鼠肝纤维化治疗作用的机制之一。

Objective To study the therapeutic effect of Interleukin-10(IL-10 ) and effects of IL-10 on expression of tumor necrosis factor-α(TNF-α),insu lin -like growth factor 1(IGF-1) and its receptors(IGF-1R) in fibrotic rat li ver .Methods Fourty SD rats were divided into control group (group N)and CCl_4-i nduced hepatic fibrosis model group, randomly. After CCl_4 had been injected for 9 weeks, the model group was divided into three groups. Rats in group S were killed death immediately, rats in group I were treated with IL-10 for two w eeks a n d then sacrificed, rats in Group R recovered without intervention two weeks, then be killed. The expression of TNF-α?IGF-1 and IGF-1R in liver tissue and th e degree of hepatic fibrosis were measured by S-P immunohistochemistry and HE staining. Results The degree of hepatic fibrosis in group I was markedly l ower than that in group S and group R,and there was no difference between group S and group R . Th e positive levels of TNF-α?IGF-1 and IGF-1R in group S were increased s ignifi cantly compared with group N (P<0.05). The positive signals decreased sig nificantl y in group I and in group R(P<0.05), but positive score was significantly lo wer in group I than that in group R (P<0.05).Conclusions Exogen ous IL-10 can inhibit the expression of TNF-α?IGF-1 and IGF-1R in fibrotic rat and this may be one o f the possible mechanism that IL-10 have some therapeutic effect on fibrotic rat.