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白藜芦醇对阿霉素诱导心肌细胞凋亡的保护作用及机制研究 认领 被引量:1

Protective effect and mechanism of resveratrol on doxorubicin-induced cardiomyocyte apoptosis
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摘要 目的:探讨白藜芦醇(RSV)对阿霉素诱导的心肌细胞凋亡的保护作用及对E2F转录因子1(E2F1)/腺苷酸活化蛋白激酶α2(AMPKα2)信号通路的影响.方法:用小干扰RNA siE2F1转染H9c2心肌细胞,将H9c2细胞分为对照组、阿霉素组、siE2F1组、阿霉素+siE2F1组、RSV组、阿霉素+RSV组,阿霉素终浓度为1μmol/L,RSV终浓度为20μmol/L.各组干预24 h后,检测E2F1、AMPKα2和胱天蛋白酶-3剪切体(cleaved caspase-3)的蛋白表达水平及心肌细胞凋亡率.结果:与对照组相比,阿霉素组E2F1、AMPKα2和cleaved caspase-3的蛋白表达水平和心肌细胞凋亡率均显著增加(P均<0.001).细胞转染后,siE2F1显著抑制E2F1的表达.与阿霉素组相比,阿霉素+siE2F1组E2F1、AMPKα2和cleaved caspase-3的蛋白表达水平及心肌细胞凋亡率显著降低(P均<0.001).RSV干预能够部分逆转阿霉素诱导的心肌细胞凋亡(P<0.001),与阿霉素组相比,阿霉素+RSV组E2F1、AMPKα2和cleaved caspase-3的蛋白表达水平显著降低(P均<0.001).结论:RSV可减轻阿霉素诱导的心肌细胞凋亡,其机制可能与抑制E2F1/AMPKα2通路的激活有关. Objective:To investigate the effects of resveratrol(RSV) on doxorubicin(DOX)-induced cardiomyocyte apoptosis and E2 F transcription factor 1(E2 F1)/AMP-activated protein kinase α2(AMPKα2) signaling pathway. Methods:A small interfering RNA siE2 F1 was used to transfect the rat cardiomyocyte cell line(H9 c2). H9 c2 cells were divided into six groups: control group, DOX group, siE2 F1 group, DOX+siE2 F1 group, RSV group and DOX+RSV group. The final concentration of DOX and RSV were 1 μmol/L and 20 μmol/L, respectively. Expression of E2 F1, AMPKα2, cleaved caspase-3 and the apoptosis rate of cardiomyocytes were detected at 24 hours after intervention in each group. Results:Compared with the control group, the expression of E2 F1, AMPKα2, cleaved caspase-3 and the apoptosis rate of cardiomyocytes significantly increased in the DOX group(P all<0.001). After transfection, siE2 F1 significantly inhibited the expression of E2 F1. Compared with the DOX group, the expression of E2 F1, AMPKα2, cleaved caspase-3 and the apoptosis rate of cardiomyocytes in DOX+siE2 F1 group significantly decreased(P all<0.001). RSV partially reversed the apoptosis of cardiomyocytes induced by DOX(P<0.001). The expression of E2 F1, AMPKα2 and cleaved caspase-3 significantly decreased in RSV+DOX group compared with the DOX group(P all<0.001). Conclusions:RSV can attenuate DOX-induced cardiomyocyte apoptosis, and its mechanism may be related to the inhibition of E2 F1/AMPKα2 pathway activation.
作者 俞健颖 潘建安 张俊峰 王长谦 顾俊 YU Jianying;PAN Jianan;ZHANG Junfeng;WANG Changqian;GU Jun(Department of Cardiology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China)
出处 《国际心血管病杂志》 2019年第6期341-345,共5页 International Journal of Cardiovascular Disease
基金 国家自然科学基金(81670293)。
关键词 阿霉素 心肌细胞 凋亡 E2F转录因子1 白藜芦醇 Doxorubicin Cardiomyocyte Apoptosis E2F transcription factor 1 Resveratrol
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