吲哚-3-原醇对猪血清诱导大鼠肝纤维化的治疗作用  

Therapeutic effect of indole-3-carbinol on pigserum-induced hepatic fibrosis in rats

作　　者：平洁[1,2] 高爱梅[1] 徐丹[1,2] 李瑞雯[1] 汪晖[1,2] 

机构地区：[1]武汉大学基础医学院药理学系,湖北武汉430071 [2]武汉大学食品与药品评价研究中心,湖北武汉430071

出　　处：《药学学报》2011年第8期915-921,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81072709;81001466);湖北省自然科学基金资助项目(2008CDBll7)

摘　　要：研究吲哚-3-原醇(I3C)对猪血清诱导大鼠肝纤维化的治疗作用及其机制。腹腔注射猪血清制备大鼠肝纤维化模型,造模成功后用I3C治疗17天。采用HE和Masson三色染色法分别观察肝脏病理学和胶原含量改变;生化比色法测定肝组织羟脯氨酸(Hyp)含量;免疫组织化学法观察肝脏中α-平滑肌肌动蛋白(α-SMA)的表达。进一步培养大鼠肝星状细胞株HSC-T6,用13C处理24 h后,FITC-Annexin V/PI双重染色法检测细胞凋亡;实时荧光定量PCR法检测细胞凋亡相关蛋白Bax和Bcl-2的mRNA表达。结果显示,与模型对照组比较,各I3C治疗组的肝组织Hyp含量不同程度降低,肝细胞损伤减轻,胶原纤维沉积减少(P<0.01),α-SMA表达降低(P<0.01)。细胞实验显示,I3C可明显增加HSC-T6细胞凋亡率,升高Bax/Bcl-2的mRNA表达(P<0.05)。以上结果说明,I3C对猪血清诱导大鼠肝纤维化有一定治疗作用,可能与其诱导活化HSC凋亡继而促进基质胶原降解有关。This study is to investigate the therapeutic effect and mechanism of indole-3-carbinol （I3C） on pigserum-induced liver fibrosis of rats. The liver fibrotic model of rats was induced by pig serum. After modelswere successfully established, rats in the treatment groups were administered with I3C through intraperitonealinjection or curcumin by intragastric administration, daily for 17 days. Hepatic hydroxyproline （Hyp） contentwas measured. The liver histology and immunohistochemistry with a-smooth muscle actin （α-SMA） wereassayed. Hepatic stellate cells line, HSC-T6 was incubated with different concentrations of I3C （25, 50,and 100 （μmol·L-1） for 24 h. The effect of I3C on cell apoptosis was identified by FITC-Annexin V/PI doublelabeled assay. And the mRNA expressions of Bax and Bcl-2 were measured by real time RT-PCR. The resultsshowed that hepatic content of Hyp decreased by I3C treatment, as compared with the fibrotic model control.Histopathological changes, such as steatosis, necrosis, deposition of collagenous fiber reduced remarkablyand the expression of α-SMA was significantly down-regulated in the I3C-treated groups （P 0.01）. Apoptosisanalysis showed that I3C significantly increased HSC-T6 apoptosis rate and the expressional ratio of Bax toBcl-2. The results indicated that I3C could effectively cure pig serum-induced liver fibrosis in vivo by inducing HSC apoptosis and promoting ECM degradation.

关 键 词：吲哚-3-原醇 肝纤维化 肝星状细胞 细胞凋亡 胶原 

分 类 号：R965[医药卫生—药理学]