白细胞介素-10对实验性肝纤维化大鼠Bax/Bcl-2表达的影响

Effect of Bax/Bcl-2 by IL-10 on Experimental Rat Hepatic Fibrosis

目的探讨白细胞介素-10(IL-10)对实验性肝纤维化大鼠Bax/Bcl-2表达的影响及外源性IL-10对肝纤维化的治疗及可能机制。方法47只SD大鼠随机分为生理盐水对照组(N组,6只)和CCl4组(Z组,41只)。至造模第9周,Z组随机分为模型组(M组,9只),自然恢复组(R组,9只)和IL-10治疗组(T组,9只);于12周末处死各组动物。免疫组织化学法和RT-PCR法检测各组大鼠肝脏Bax/Bcl-2的表达。结果成功建立肝纤维化模型。T组肝细胞变性及坏死程度较M组减轻;R组肝脏炎症活动度较M组有所缓解,但肝纤维化程度未见明显改善。免疫组织化学提示,Bax主要表达在肝细胞质内,Bcl-2主要表达在汇管区及纤维间隔区。组织蛋白及mRNA表达检测均显示,M组Bax较N组增高(P<0.01),Bcl-2表达亦显著增高;R组Bax表达较M组降低(P<0.01),但Bcl-2表达则较M组显著升高;T组Bax/Bcl-2均较R组显著降低。结论肝纤维化过程肝脏Bax/Bcl-2表达增强;外源性IL-10可以减轻CCl4诱导的肝脏纤维化,IL-10抗纤维化作用可能是通过减少肝细胞表达Bax、抑制肌成纤维细胞样细胞表达Bcl-2实现的。

Objective To study the expression of Bax/Bcl-2 in rat hepatic fibrosis and study the antifibrogenic role of IL-10. Methods 47 SD rats were randomly divided into two groups,normal control group（GN,6 rats） and CCl4 group（GC,41 rats）. At the end of 9th week, rats in GC were randomly allocated into three groups, model group（GM,9 rats）, IL-10 treated group（GT, 9 rats） and natural recovered group（GR,9 rats）. Rats in GM were sacrificed at the end of 9th week and rats in GT and GR were sacrificed at 12th week. Reverse-transcription polymerase chain reaction（RT-PCR） was used to analyze Bax/ Bcl-2 mRNA from freshly isolated liver cells. Immunohistochemistry was performed to detect Bax/Bcl-2 protein expression in liver tissue. Results Rat hepatic fibrosis was developed as showed by histological examination, the degree of hepatic fibrosis in GT alleviated obviously compared to GM, and the change in GR was not distinct. Both immunohistochemistry and RT-PCR showed： the expression of Bax was increased markly in GM and GR group than GT group（P〈0.01）. Bcl-2 expression was also up-regulated than GT group as well. Bax/Bcl-2 protein detection indicated GT was lower than GR（P〈0.01）. Conclusion Bax/Bcl-2 expression was both up-regulated during the process of hepatic fibrosis. Exogenous IL-10 may have an antifibrogenic and protecting effect through reducing Bax expression and Bcl-2 expression.