维甲酸相关孤核受体α(RORα)在奥曲肽抗大鼠肝纤维化中的作用

摘要

目的 观察奥曲肽(OCT)对实验性肝纤维化大鼠肝组织病理学及肝脏血清学的影响,探究维甲酸相关孤核受体α(RORα)在奥曲肽抗大鼠肝纤维化的作用.方法 将36只雄性SD大鼠随机分成3组:对照组、模型组、OCT组.实验采用四氯化碳( CCl4)建立肝纤维化模型(模型组和OCT组),饲养8周后处死大鼠并随机采集标本,使用HE及VG染色法观察大鼠肝细胞的病理改变;检测大鼠血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、透明质酸(HA)、大鼠层粘连蛋白(LN)、大鼠Ⅲ型前胶原氨基端原肽(PⅢNP)、大鼠IV型胶原(COL4)含量;使用Ishak评分系统分析各组肝细胞的炎症活动度及纤维化程度;Western blot法检测肝组织RORα受体的表达情况.结果 与对照组比较,模型组和OCT治疗组大鼠肝脏细胞的病理变化程度、肝脏炎症活动度、肝脏纤维化程度、肝脏血清AST、ALT 、HA、LN、PⅢNP、COL4 含量均显著上升,RORα显著下降(P＜0.01).与模型组比较, OCT治疗组大鼠肝脏细胞的病理变化程度、肝脏炎症活动度、肝脏纤维化程度、肝脏血清 AST、ALT、HA、LN、PⅢNP、COL4含量显著下降,RORα下降程度降低(P＜0.05).结论 OCT可降低大鼠体内RORα的下降程度,减少肝功能损害及肝纤维化程度,治疗实验性大鼠肝纤维化效果确切.%Objective To observe the effect of octreotide ( OCT) on liver histopathology and liver serology in ex-perimental hepatic fibrosis rats, and explore the role of RORα in this animal model. Methods Thirty-six male SD rats were randomly divided into three groups: control group, model group and OCT group. The model of hepatic fi-brosis was established by CCl4( model group and OCT group) . At the end of 8 week, the rats were killed and ran-domly collected. The pathological changes of liver were observed by HE and VG staining. The levels of AST, ALT, HA, LN, PⅢNP and COL4 were detected. The degree of hepatic fibrosis and the degree of inflammatory activity in each group were analyzed by Ishak scoring system. The expression of RORα receptor in liver tissue was detected by Western blot. Results Compared with the control group, the levels of hepatic pathological changes, inflammatory activity, fibrosis, serum AST, ALT, HA, LN, PⅢNP and COL4 in model group and OCT group were significantly increased and RORα significantly decreased (P＜0.01). Compared with the model group, the liver pathological changes, inflammatory activity, fibrosis, serum AST, ALT, HA, LN, PⅢNP and COL4 in OCT treatment group decreased significantly and the expression of RORα decreased ( P＜0.05) . Conclusion OCT can reduce the de-gree of hepatic fibrosis and improve liver function in rats, and its mechanism may relate to the decrease of RORα.