摘要
目的基于Nrf2-ARE信号通路探讨异甘草酸镁对雷公藤甲素损伤L-02细胞的保护作用及相关机制。方法体外培养正常人肝L-02细胞,通过免疫荧光技术检测异甘草酸镁(60μmol·L^-1)对雷公藤甲素(80nmol·L^-1)损伤L-02细胞中Nrf2核转移的影响;采用Western blotting测定细胞核中Nrf2及细胞中细胞色素P450 3A4(CYP3A4)、多药耐药相关蛋白2(multidrug resistance associated protein 2,MRP2)和胆盐输出泵(bile salt export pump,BSEP)的蛋白表达。结果雷公藤甲素对L-02细胞核中Nrf2具有诱导作用(P<0.01),并促进Nrf2核内转移;异甘草酸镁预处理组较雷公藤甲素组降低L-02细胞核中Nrf2的表达(P<0.01);异甘草酸镁预处理后对雷公藤甲素损伤L-02细胞中CYP3A4、MRP2和BSEP蛋白表达具有诱导作用(P<0.01)。结论异甘草酸镁可减轻雷公藤甲素对L-02细胞造成的损伤作用,其机制可能与诱导细胞核中Nrf2以及细胞中CYP3A4、MRP2和BSEP受体有关。
OBJECTIVE To study on the protective effect of magnesium isoglycyrrhizinate on L-02 cells injured by triptolide and its mechanism based on Nrf2-ARE signaling pathway.METHODS Human hepatocyte L-02 were cultured in vitro.Effect of magnesium isoglycyrrhizinate(60 μmol·L^-1) on nuclear translocation of nuclear factor-E2-related factor 2(Nrf2) in triptolide-induced(80 nmol·L^-1) L-02 cells by immunofluorescence;effect of magnesium isoglycyrrhizinate on the protein expression of Nrf2 in nuclear and cytochrome P450 3 A4(CYP3 A4),multidrug resistance associated protein 2(MRP2) and bile salt export pump(BSEP) in cell were determined by Western blotting.RESULTS Triptolide up-regulated the protein expression of Nrf2(P<0.01),and induced Nrf2 transfered to the triptolide-induced L-02 cell nuclear.Compared with triptolide group,magnesium isoglycyrrhizinate could obviously decrease the protein expression of Nrf2 in nuclear(P<0.01).Magnesium isoglycyrrhizinate up-regulated the protein expression of CYP3 A4,MRP2 and BSEP in triptolide-induced L-02 cell(P<0.01).CONCLUSION Magnesium isoglycyrrhizinate can alleviate the damage of L-02 cells induced by triptolide,which may be related to the induction of Nrf2 receptors in the nucleus,CYP3 A4,MRP2 and BSEP receptors in cells.
作者
谭亲友
刘兵
张靖
胡骞
朱胜楠
苏华珍
黄少远
刘芳
TAN Qinyou;LIU Bing;ZHANG Jing;HU Qian;ZHU Shengnan;SU Huazhen;HUANG Shaoyuan;LIU Fang(The Affiliated Hospital of Guilin Medical University,Clinical Pharmacy&Pharmacology Research Institute,Guilin 541001,China;The Affiliated Hospital of Guilin Medical University,Department of Hepatobiliary Surgery,Guilin 541001,China;China-USA Lipids in Health and Disease Research Center,Guilin Medical University,Guilin 541001,China;Shanghai Livzon Pharmaceutical Co.,Ltd.,Shanghai 201206,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2020年第2期138-142,共5页
Chinese Journal of Modern Applied Pharmacy
基金
国家自然科学基金项目(81360665,81760747)
广西自然科学基金项目(2015GXNSFAA139114,2013GXNSFBA019174)
广西壮族自治区卫生厅中医药攻关课题(GZGG13-08)
