Nrf2通路在齐墩果酸所致肝纤维化中的作用研究（英文）

Role of Nrf2 pathway on hepatic fibrosis induced by oleanolic acid

目的以HSC-T6细胞为模型,研究Nrf2通路对齐墩果酸所致肝纤维化的影响。方法设置空白组、低剂量组(10μmol/L)、中剂量组(20μmol/L)、高剂量组(40μmol/L),给予齐墩果酸24 h后检测α-SMA与核内Nrf2蛋白表达以及Ⅰ型胶原含量;分别采用siRNA沉默、Sulforaphane(SFN)激动Nrf2后,给予齐墩果酸,检测α-SMA与核内Nrf2蛋白表达以及Ⅰ型胶原含量的变化。结果 (1)给予齐墩果酸后,核内Nrf2蛋白表达上调,中高剂量组α-SMA蛋白表达上调,Ⅰ型胶原含量明显增多;(2)空白组与低剂量组采用siRNA沉默Nrf2后,α-SMA蛋白表达上调、Ⅰ型胶原含量增多,高剂量组采用siRNA沉默Nrf2后,α-SMA蛋白表达下调,Ⅰ型胶原含量减少;(3)给予5μmol/L SFN激动Nrf2后,α-SMA蛋白表达下调,与Ⅰ型胶原含量降低。结论 Nrf2通路可以抑制齐墩果酸所致的肝纤维化。

Objective To investigate the effect of Nrf2 pathway on hepatic fibrosis induced by oleanolic acid using HSC-T6 cells as the model. Methods Blank Group,Low-dose Group（ 10 μmol/l）,Middle-dose Group（ 20 μmol/l） and High-dose Group（ 40 μmol/l） were administered with oleanolic acid,and then the α-SMA and intranuclear Nrf2 protein expression and type I collagen content were detected after 24 h. SiRNA was used to silence Nrf2 and sulforaphane（ SFN） was used to activate Nrf2,and then oleanolic acid was administered to detect α-SMA and intranuclear Nrf2 protein expression and the changes of type I collagen content. Results（1） After administration of oleanolic acid,the expression of intranuclear Nrf2 protein was up-regulated,the expression of α-SMA protein was up-regulated and the typeⅠ collagen content was significantly increased in Middle-dose Group and High-dose Group.（2）After siRNA silencing Nrf2 was adopted in the Blank Group and Low-dose Group,the expression of α-SMA protein was up-regulated and typeⅠcollagen content was increased. After siRNA silencing Nrf2 was adopted in the High-dose Group,the expression of α-SMA protein was down-regulated and typeⅠ collagen content was decreased.（3）After 5 μmol/l SFN was administrated to activate Nrf2,α-SMA protein expression was down-regulated and type I collagen content was decreased. Conclusion The Nrf2 pathway plays a protective role in the process of hepatic fibrosis induced by oleanolic acid.