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引用本文:谭亲友,刘兵,张靖,胡骞,朱胜楠,苏华珍,黄少远,刘芳.基于Nrf2信号通路探讨异甘草酸镁对雷公藤甲素损伤L-02细胞中相关蛋白表达的影响[J].中国现代应用药学,2020,37(2):138-142.
TAN Qinyou,LIU Bing,ZHANG Jing,HU Qian,ZHU Shengnan,SU Huazhen,HUANG Shaoyuan,LIU Fang.Effect of Magnesium Isoglycyrrhizinate on Expression of Related Proteins in Triptolide-injured L-02 Cells Based on Nrf2 Signaling Pathway[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(2):138-142.
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基于Nrf2信号通路探讨异甘草酸镁对雷公藤甲素损伤L-02细胞中相关蛋白表达的影响
谭亲友1,2,3, 刘兵4, 张靖1, 胡骞1, 朱胜楠1,2, 苏华珍1, 黄少远1, 刘芳1
1.桂林医学院附属医院临床药学与临床药理学教研室, 广西 桂林 541001;2.桂林医学院附属医院肝胆胰外科实验室, 广西 桂林 541001;3.桂林医学院中美健康与疾病脂质研究中心, 广西 桂林 541001;4.上海丽珠制药有限公司, 上海 201206
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(60 μmol·L-1)对雷公藤甲素(80 nmol·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 associatedprotein 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。
关键词:  Nrf2信号通路  异甘草酸镁  雷公藤甲素  L-02细胞
DOI:10.13748/j.cnki.issn1007-7693.2020.02.003
分类号:R285.5
基金项目: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)
Effect of Magnesium Isoglycyrrhizinate on Expression of Related Proteins in Triptolide-injured L-02 Cells Based on Nrf2 Signaling Pathway
TAN Qinyou1,2,3, LIU Bing4, ZHANG Jing1, HU Qian1, ZHU Shengnan1,2, SU Huazhen1, HUANG Shaoyuan1, LIU Fang1
1.The Affiliated Hospital of Guilin Medical University, Clinical Pharmacy & Pharmacology Research Institute, Guilin 541001, China;2.The Affiliated Hospital of Guilin Medical University, Department of Hepatobiliary Surgery, Guilin 541001, China;3.China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin 541001, China;4.Shanghai Livzon Pharmaceutical Co., Ltd., Shanghai 201206, China
Abstract:
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 3A4(CYP3A4), 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 CYP3A4, 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, CYP3A4, MRP2 and BSEP receptors in cells.
Key words:  Nrf2 pathway  magnesium isoglycyrrhizinate  triptolide  L-02 cell
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