陈亚武, 金屏, 王少玮, 郝瑞军, 刘金成, 郭红. Adiponectin 通过FoxO1信号通路减轻阿霉素细胞毒性的作用机制研究[J]. 心脏杂志, 2021, 33(2): 127-132. DOI: 10.12125/j.chj.202008066
    引用本文: 陈亚武, 金屏, 王少玮, 郝瑞军, 刘金成, 郭红. Adiponectin 通过FoxO1信号通路减轻阿霉素细胞毒性的作用机制研究[J]. 心脏杂志, 2021, 33(2): 127-132. DOI: 10.12125/j.chj.202008066
    shu
    Ya-wu CHEN, Ping JIN, Shao-wei WANG, Rui-jun HAO, Jin-cheng LIU, Hong GUO. Protective role of Adiponectin on FoxO1-dependent autophagy against doxorubicin-induced cardiotoxicity[J]. Chinese Heart Journal, 2021, 33(2): 127-132. DOI: 10.12125/j.chj.202008066
    Citation: Ya-wu CHEN, Ping JIN, Shao-wei WANG, Rui-jun HAO, Jin-cheng LIU, Hong GUO. Protective role of Adiponectin on FoxO1-dependent autophagy against doxorubicin-induced cardiotoxicity[J]. Chinese Heart Journal, 2021, 33(2): 127-132. DOI: 10.12125/j.chj.202008066
    shu

    Adiponectin 通过FoxO1信号通路减轻阿霉素细胞毒性的作用机制研究

    Protective role of Adiponectin on FoxO1-dependent autophagy against doxorubicin-induced cardiotoxicity

      摘要
    • 摘要:
        目的  阐明FoxO1在脂联素（Adiponectin，APN）减轻阿霉素（Doxorubicin，DOX）心肌细胞毒性中的作用及机制。
        方法  将分离的乳鼠心肌原代细胞（Neonatal rat cardiomyocytes, nrCMs）随机分为对照组（CON）、APN处理组（APN）、DOX损伤组（DOX）、APN保护组（APN-DOX）、DOX损伤+Scramble siRNA组（DOX-Scramble siRNA）、DOX-FoxO1 siRNA组、APN-DOX-Scramble siRNA组、APN-DOX-FoxO1 siRNA组。以CCK-8试剂盒检测细胞活力、ATP检测试剂盒检测线粒体ATP生成、ROS检测试剂盒检测ROS生成量、Western blot检测自噬标志蛋白的表达情况。
        结果  DOX处理后较CON组，细胞活力显著降低（P<0.05），线粒体ATP生成受到抑制，同时ROS生成量显著增加，自噬被显著激活（P<0.05）；APN预处理可通过抑制自噬而显著降低DOX诱导的心肌细胞毒性（P<0.05），APN可通过上调phospho-FoxO1的表达而抑制自噬的激活，从而保护nrCMs细胞免受DOX诱导的心肌细胞毒性损伤，APN的心肌保护作用可被FoxO1 siRNA而抑制，如自噬过程的激活及ATP生成受到抑制，同时ROS生成量显著增加。
        结论  APN通过上调FoxO1磷酸化水平，抑制自噬，进而缓解DOX引起的心肌细胞毒性。

       

      Abstract:
        AIM  To elucidate the mechanism of foxO1 signaling pathway in the protective role of adiponectin (APN) against doxorubicin-induced cardiotoxicity.
        METHODS  Neonatal rat cardiomyocytes (nrCMs) were randomly divided into the following groups: CON, APN, APN-DOX, DOX-Scramble siRNA, DOX-FoxO1 siRNA, APN-DOX-Scramble siRNA, and APN-DOX-FoxO1 siRNA. Cell viability was detected by CCK-8 kit, mitochondrial ATP production was detected by ATP detection kit, ROS production was detected by ROS detection kit, and autophagy marker protein expression was detected by Western blot.
        RESULTS  Compared with CON group, DOX treatment significantly decreased cell viability and mitochondrial ATP production but increased ROS production and activated autophagy (P<0.05). APN pretreatment significantly reduced DOX induced cardiotoxicity by inhibiting autophagy. In terms of the mechanism of the protective role of APN against Dox-induced cardiotoxicity, we found that APN inhibited the activation of autophagy by up-regulating the expression of phospho FoxO1, thus protecting nrCMs cells from DOX-induced cardiotoxicity. However, the myocardial protective effect of APN was abolished by FoxO1 siRNA treatment, such as the inhibition of autophagy and ATP production, and the increase of ROS production.
        CONCLUSION  APN attenuates DOX induced cardiotoxicity by up-regulating foxO1 phosphorylation and inhibiting autophagy activation.

       

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