Nrf2在肝纤维化小鼠肝细胞中的核转移

Nuclear translocation of Nrf2 in hepatocytes of mice with hepatic fibrosis

目的:研究肝纤维化小鼠肝细胞中核因子相关因子-2(NF-E2-related factor 2,Nrf2)核转移情况.方法:实验小鼠随机分为正常对照组(normal control,NC组)、模型组,每组8只.模型组腹腔注射四氯化碳(CCl4)石蜡油溶液建造肝纤维化模型,NC组给予同体积矿物油腹腔注射,共10wk.收集肝脏标本HE染色及Masson染色观察肝脏炎症和纤维化程度;Western blot检测细胞内Nrf2、醌氧化还原酶1(quinone oxidoreductase,Nqo1)总蛋白及Nrf2核蛋白表达情况.结果:随CCl4肝损伤时间延长,组织病理学结果显示模型组明显炎症反应及纤维间隔形成;Western blot结果显示,与NC组Nrf2、Nqo1总蛋白及Nrf2核蛋白表达量分别为0.490±0.088、0.430±0.057、0.370±0.022比较,模型组为0.790±0.045、0.720±0.040、0.670±0.044显著增高,差异具有统计学意义(F=2.027、0.772、1.552,P<0.05).结论:肝纤维化小鼠肝细胞中Nrf2核转移增多并上调细胞保护性蛋白Nqo1表达.

AIM： To investigate the nuclear translocation of NF-E2-related factor 2 （Nrf2） in hepatocytes of mice with hepatic fibrosis. METHODS： Mice were randomly divided into two groups： normal control group and model group. For the model group, carbon tetrachlo-ride （CCl4 ） dissolved in mineral oil was injected intraperitoneally for 10 wk, while the normal control group was injected with the samevolume of mineral oil. At the end of the 10th week, specimens were collected to assess the degrees of hepatic fibrosis and inflammation by haematoxylin-eosin staining and Masson staining. Western blot was used to detect the protein expression of Nrf2 and NAD（P）H quinine oxido-reductase 1 （Nqo1） and nuclear translocation of Nrf2. RESULTS： Compared to the normal control group, the degrees of hepatic inflammation and fibrosis in the model group were significantly increased. Western blot analysis showed that, compared to the normal control group （0.490 ± 0.088, 0.430 ± 0.057, 0.370 ± 0.022）, the expression levels of Nrf2 and Nqo1 proteins, as well as nuclear translocation of Nrf2 were increased significantly in the model group （0.490 ± 0.088 vs 0.790 ± 0.045, 0.430 ± 0.057 vs 0.720 ± 0.040, 0.370 ± 0.022 vs 0.670 ± 0.044; F = 2.027, 0.772, 1.552, all P 0.05）. CONCLUSION： In mice with hepatic fibrosis, the nuclear translocation of Nrf2 in hepatocytes is increased to up-regulate its target protein Nqo1.