激活转录因子nrf2对肝细胞胰岛素抵抗的影响及信号通路
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摘 ,2019,19(80):55-57.
Effect of Activating Transcription Factor Nrf2 on Human Hepatocyte Insulin Resistance and Signaling Pathway
LI Qiang, ZHANG Ding, SHI Xi-yun, CHENG Yan-hui, WANG Bao-jian*
世界最新医学信息文摘 2019 年第 19 卷第 80 期
55ห้องสมุดไป่ตู้
·论著·
激活转录因子 Nrf2 对肝细胞胰岛素抵抗的影响及信号通路
李强，张鼎，师喜云，程艳慧，王保健 *
（联勤保障部队第 988 医院，河南 郑州）
摘要：目的 转录因子 Nrf2 在保护细胞对抗氧化损害时发挥重要作用，姜黄提取物（Curcumin， Cur）可上调细胞抗氧化酶的表达。本研究 拟探讨 Cur 在肝脏细胞中能否通过诱导 Nrf2 核转位发挥抗氧化作用并进而减轻其胰岛素抵抗（Insulin resistance，IR）。方法 人肝细胞系 L02 被分成 4 组，分别正常培养（Control 组）、与葡萄糖氧化酶（Glucose oxidase）共培养（GO 组）、与 Cur 及 GO 共培养（Cur+GO 组）、与 Wortmannin（Wor）和 Cur 及 GO 共培养（Cur+GO+Wor 组）后，分别检测细胞氧化水平、细胞损害程度、Nrf2 核转位状况及 IR 水平。结果 GO 共培养后显著增加了人肝细胞 ROS、MDA、LDH 及 AST 浓度，减低了 GSH 浓度，诱导肝细胞 IR。L02 使用 Cur 预处理后再与 GO 共培 养能够减低 GO 引起的肝细胞损害所致指标升高，并能有效减低 GO 引起细胞内脂质过氧化及 IR，这与 Cur 产生的促进 Nrf2 核转位效应一致。 Wor 能部分抑制 Cur 诱导的 Nrf2 核转位。结论 Cur 能够减低 ROS 导致的人肝细胞 IR，可能是通过促进 Nrf2 核转位发挥作用。 关键词：姜黄提取物；肝细胞 L02；氧化损害；胰岛素抵抗 中图分类号：R458+.5 文献标识码：A DOI: 10.19613/ki.1671-3141.2019.80.025 本文引用格式：李强 , 张鼎 , 师喜云 , 等 . 激活转录因子 Nrf2 对肝细胞胰岛素抵抗的影响及信号通路 [J]. 世界最新医学信息文
(Department of Internal Medicine, NO.988th Hospital of PLA, Zhengzhou Henan)
ABSTRACT: Objective Nrf2 is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin(Cur) has been reported to upregulate the expression of numerous reactive oxygen species (ROS) detoxifying genes in cells. This study was designed to investigate whether Cur could induced Nrf2 nuclear translocation and reduce ROS-mediated insulin resistance(IR) in cultured hepatocytes. Methods Human L02 hepatocytes were divided into four groups. Cells in Control group were incubated without special. Cells in GO group were incubated with glucose oxidase(GO). Cells in Cur+GO group were incubated with GO and Cur. Cells in Cur+GO+Wor group were incubated with GO, Cur and Wortmannin(Wor, PI3K inhibitor). Then oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. Results GO exposure significantly increased ROS, MDA, LDH and AST level, as well as causing IR. Cur pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and IR induced by GO in L02 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by Cur. Wor partially blocked Cur -induced Nrf2 nuclear translocation. Conclusion These findings suggest that Cur could reduce ROS-mediated IR in hepatocytes, at least in part through nuclear translocation of Nrf2. KEY WORDS: Curcumin; L02 hepatocytes; Oxidative stress; Insulin resistance
Effect of Activating Transcription Factor Nrf2 on Human Hepatocyte Insulin Resistance and Signaling Pathway
LI Qiang, ZHANG Ding, SHI Xi-yun, CHENG Yan-hui, WANG Bao-jian*
世界最新医学信息文摘 2019 年第 19 卷第 80 期
55ห้องสมุดไป่ตู้
·论著·
激活转录因子 Nrf2 对肝细胞胰岛素抵抗的影响及信号通路
李强，张鼎，师喜云，程艳慧，王保健 *
（联勤保障部队第 988 医院，河南 郑州）
摘要：目的 转录因子 Nrf2 在保护细胞对抗氧化损害时发挥重要作用，姜黄提取物（Curcumin， Cur）可上调细胞抗氧化酶的表达。本研究 拟探讨 Cur 在肝脏细胞中能否通过诱导 Nrf2 核转位发挥抗氧化作用并进而减轻其胰岛素抵抗（Insulin resistance，IR）。方法 人肝细胞系 L02 被分成 4 组，分别正常培养（Control 组）、与葡萄糖氧化酶（Glucose oxidase）共培养（GO 组）、与 Cur 及 GO 共培养（Cur+GO 组）、与 Wortmannin（Wor）和 Cur 及 GO 共培养（Cur+GO+Wor 组）后，分别检测细胞氧化水平、细胞损害程度、Nrf2 核转位状况及 IR 水平。结果 GO 共培养后显著增加了人肝细胞 ROS、MDA、LDH 及 AST 浓度，减低了 GSH 浓度，诱导肝细胞 IR。L02 使用 Cur 预处理后再与 GO 共培 养能够减低 GO 引起的肝细胞损害所致指标升高，并能有效减低 GO 引起细胞内脂质过氧化及 IR，这与 Cur 产生的促进 Nrf2 核转位效应一致。 Wor 能部分抑制 Cur 诱导的 Nrf2 核转位。结论 Cur 能够减低 ROS 导致的人肝细胞 IR，可能是通过促进 Nrf2 核转位发挥作用。 关键词：姜黄提取物；肝细胞 L02；氧化损害；胰岛素抵抗 中图分类号：R458+.5 文献标识码：A DOI: 10.19613/ki.1671-3141.2019.80.025 本文引用格式：李强 , 张鼎 , 师喜云 , 等 . 激活转录因子 Nrf2 对肝细胞胰岛素抵抗的影响及信号通路 [J]. 世界最新医学信息文
(Department of Internal Medicine, NO.988th Hospital of PLA, Zhengzhou Henan)
ABSTRACT: Objective Nrf2 is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin(Cur) has been reported to upregulate the expression of numerous reactive oxygen species (ROS) detoxifying genes in cells. This study was designed to investigate whether Cur could induced Nrf2 nuclear translocation and reduce ROS-mediated insulin resistance(IR) in cultured hepatocytes. Methods Human L02 hepatocytes were divided into four groups. Cells in Control group were incubated without special. Cells in GO group were incubated with glucose oxidase(GO). Cells in Cur+GO group were incubated with GO and Cur. Cells in Cur+GO+Wor group were incubated with GO, Cur and Wortmannin(Wor, PI3K inhibitor). Then oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. Results GO exposure significantly increased ROS, MDA, LDH and AST level, as well as causing IR. Cur pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and IR induced by GO in L02 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by Cur. Wor partially blocked Cur -induced Nrf2 nuclear translocation. Conclusion These findings suggest that Cur could reduce ROS-mediated IR in hepatocytes, at least in part through nuclear translocation of Nrf2. KEY WORDS: Curcumin; L02 hepatocytes; Oxidative stress; Insulin resistance