| 程妮 曾迪 陈焱 丁璐 李晓莉 赵天智 郑强荪.雌激素膜受体GPER1 通过调节Nrf2 减轻心肌氧化损伤[J].,2016,16(10):1807-1811 |
| 雌激素膜受体GPER1 通过调节Nrf2 减轻心肌氧化损伤 |
| G Protein-Coupled Estrogen Receptor 1 Mediates ProtectionAgainst Oxidative Stress-induced Cardiomyocyte Injuryby Upregulating Nrf2 Expression |
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| DOI： |
| 中文关键词: GPER1 PI3K/Akt信号通路 Nrf2 抗氧化作用 |
| 英文关键词: GPER1 PI3K/Akt signaling pathway Nrf2 Antioxidative effect |
| 基金项目:国家自然科学基金项目（81200902）；中国博士后科学基金项目（2014T70986）；陕西省自然科学基金项目（S2015YFJQ1250） |
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| 中文摘要: |
| 目的：观察雌激素膜受体GPER1 对心肌细胞氧化损伤的保护作用，并探讨其通过PI3K/Akt 信号通路上调Nrf2，减轻心肌氧
化损伤的机制。方法：H2O2处理原代培养的新生大鼠心肌细胞建立氧化损伤模型，分为对照组、H2O2处理组，GPER1 受体激动剂
G1 预处理+H2O2处理组和GPER1 拮抗剂G15+G1 预处理+H2O2 处理组，MTT 检测细胞活性，Hoechst33342 染色和cleaved
caspase-3免疫荧光染色观察细胞凋亡，并检测细胞内氧自由基，总抗氧化能力，超氧化物歧化酶（SOD）和丙二醛（MDA）的水平。
Western blot测定细胞中p-Akt和细胞核内Nrf2 的水平。结果：G1 显著抑制H2O2导致细胞活性下降和细胞凋亡，并降低细胞内氧
自由基水平，提高总抗氧化能力，增加SOD活性，减少MDA含量，但G15 能拮抗G1 的上述效应。同时G1 能增加细胞内Akt 磷
酸化水平和细胞核内Nrf2 的表达，这些效应可被G15 和LY-294002 阻断。结论：GPER1 通过PI3K/Akt信号通路，调节Nrf2 的表
达，抑制氧化应激导致的心肌细胞损伤。GPER1 可以作为开发心肌缺血损伤保护剂的一个潜在靶点。 |
| 英文摘要: |
| Objective:To investigate the cardioprotection effects mediated by G Protein-Coupled Estrogen Receptor 1 (GPER1)
and the mechanism of inhibition of oxidative damage by upregulating Nrf2 expression via PI3K/Akt signaling pathway.Methods:H2O2-induced injury in neonatal rat cardiomyocytes in vitro to simulate the oxidative damage following myocardial ischemia/reperfusion.
The neonatal rat cardiomyocytes were divided into control group, H2O2 treation group, G1-pretreation before H2O2 exposure group and
G15 treated and then G1-pretreation before H2O2 exposure group. Cell viability was assessed by MTT assay and cell apoptosis was
assessed by Hoechst33342 staining and immunofluorescence staining for cleaved caspase-3. In addition, intracellular oxygen free
radicals, total antioxidant capacity, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected. Further, the
phosphorylation of Akt and Nrf2 level in rat cardiomyocytes were determined by Western blot analyses.Results:G1 significantly
inhibited the decrease in cell activity and cell apoptosis, reduced the level of oxygen free radicals and MDA, improved the total
antioxidant capacity, and increased SOD activity in H2O2-treated neonatal rat cardiomyocytes, all of which were markedly attenuated by
G15. Further, activation of GPER1 increases the phosphorylation of Akt and Nrf2 level in neonatal rat cardiomyocytes after H2O2
exposure，which were abolished by G15 and LY-294002.Conclusion:Activation of GPER1 protects neonatal rat cardiomyocytes against
H2O2-induced cell injury by upregulating Nrf2 expression via PI3K/Akt signaling pathway. GPER1 may be a potential target to prevent
myocardial ischemia injury. |
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