白细胞介素10通过促进线粒体自噬调节心肌细胞生物氧化
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(1.南华大学附属第二医院心血管内科,湖南省衡阳市 421001;2.中山大学孙逸仙纪念医院心血管内科, 广东省广州市 510120;3.中山大学孙逸仙纪念医院内分泌科,广东省广州市 510120)

作者简介:

林永青,学士,主治医师,研究方向为心血管介入治疗,E-mail为linyq1213@126.com。通信作者田国平,博士,教授,主任医师,研究方向为心肌细胞物质代谢机制,E-mail为1164385050@qq.com。

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基金项目:

国家自然科学基金项目(81300071);广东省自然科学基金项目(2014A030313049);广州市科技计划项目(201510010048、201510010050)


Interlekutin-10 promotes oxidative phosphorylation via inducing mitophagy in cardiomyocytes
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1.Department of Cardiovascular Medicine, the Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China;2.Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University,Guangzhou, Guangdong 510120, China;3.Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China)

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    摘要:

    目的 探讨白细胞介素10(IL-10)对心肌细胞葡萄糖代谢的影响及其可能机制。方法 使用棕榈酸干预复制心肌脂毒性和葡萄糖利用减少细胞模型,外源性IL-10干预后,以荧光标记的2-脱氧葡萄糖(2-NBDG)摄入法检测心肌细胞的葡萄糖摄取,检测乳酸及体外氧化磷酸分别代表葡萄糖无氧酵解及有氧氧化水平;使用免疫荧光检测线粒体自噬;使用Real-Time PCR及Western Blot检测线粒体自噬关键基因PINK1表达。结果 与对照组比较,IL-10处理后,心肌细胞摄入2-NBDG量约增加1倍;细胞培养上清乳酸含量减少近80%;细胞内乳酸含量亦显著减少。IL-10促进微管相关蛋白1轻链3-绿色荧光蛋白(LC3-GFP)在心肌细胞线粒体聚集,促进线粒体自噬,并上调PTEN诱导假定激酶1(PINK1)表达。结论 IL-10通过促进葡萄糖转入及氧化磷酸化恢复心肌细胞供能物质组成;其对氧化磷酸化的作用可能是通过上调PINK1进而促进线粒体自噬实现的。

    Abstract:

    Aim To investigate the role of interlekutin-10 (IL-10) in cardiomyocyte metabolism. MethodsCardiomyocyte lipotoxicity and glucose utilization reduction was induced by palmitate. Cardiomyocytes were treated with IL-10 and 2-NBDG uptake assay was adopted to assess the glucose utilization in cells. Lactic acid and oxidative phosphorylation were used to assess glycolysis and oxidation of glucose, respectively. Immuno-fluorescence was used to evaluate mitophagy in cardiomyocytes. RT-qPCR and Western blot were used to detect PINK1 expression. Results Compared with the control, IL-10 treatment approximately doubled the amount of 2-NBDG in cardiomyocytes. The supernatant and intracellular lactic acid were both reduced. Moreover, LC3-GFP was enhanced in mitochondrial aggregation and the PINK1 expression was up-regulated, which indicated mitophagy increase in cardiomyocytes. Conclusion IL-10 may re-balance cardiomyocytes metabolism substrates by increasing glucose utilization, glycolysis and oxidative phosphorylation through inducing mitophagy mediated by PINK1 up-expression.

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林永青,梁颖,张海峰,田国平.白细胞介素10通过促进线粒体自噬调节心肌细胞生物氧化[J].中国动脉硬化杂志,2019,27(5):381~385.

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  • 收稿日期:2018-12-08
  • 最后修改日期:2019-03-03
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  • 在线发布日期: 2019-04-08