南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (1): 45-51.doi: 10.12122/j.issn.1673-4254.2024.01.06

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白藜芦醇可减轻高糖诱导的心肌细胞肥大：基于促进SIRT1表达维持线粒体稳态

叶红伟，张钰明，云 琦，杜若丽，李 璐，李玉萍，高 琴   

  1. 蚌埠医科大学生理学教研室，心脑血管疾病基础与临床蚌埠医科大学重点实验室，安徽 蚌埠 233000
  • 发布日期:2024-01-24

Resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by maintaining mitochondrial homeostasis via enhancing SIRT1 expression

YE Hongwei, ZHANG Yuming, YUN Qi, DU Ruoli, LI Lu, LI Yuping, GAO Qin   

  1. Department of Physiology, Key Laboratory of Basic and Clinical Cardiovascular Diseases, Bengbu Medical University, Bengbu 233000, China
  • Published:2024-01-24

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摘要： 目的 探讨白藜芦醇是否通过促进沉默信息调节因子2同源体1（SIRT1）表达调控线粒体稳态，减轻高糖诱导的H9c2心肌细胞肥大。方法 将对数生长的H9c2心肌细胞随机分为4组：正常糖浓度组（NG组）、高糖组（HG组）、高糖+白藜芦醇组（HG+RES组）、高糖+白藜芦醇+SIRT1基因干扰组（HG+RES+si-SIRT1组）。各组细胞培养72 h后，检测细胞超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量，检测细胞活性氧（ROS）水平，计算细胞相对面积，检测心房利钠因子（ANF）和脑钠肽（BNP）mRNA表达，SIRT1蛋白、线粒体融合相关蛋白视神经萎缩蛋白1（OPA1）和线粒体融合蛋白2（MFN2）、线粒体分裂相关蛋白线粒体动力相关蛋白1（DRP1）和线粒体分裂蛋白1（FIS1）以及线粒体自噬相关蛋白BNIP3L和LC3的表达。结果 与NG组相比，HG组心肌细胞SOD活力降低（P<0.01），MDA含量和ROS水平升高，细胞相对面积增加，ANF和BNP mRNA表达增加，SIRT1、OPA1、MFN2和BNIP3L蛋白表达降低，LC3-II/LC3-I比值降低，DRP1和FIS1蛋白表达增高（P<0.01）；与HG组相比，HG+RES组SOD活力升高，MDA含量和 ROS水平降低，细胞相对面积减少，ANF和BNP mRNA表达下降，SIRT1、OPA1、MFN2和BNIP3L蛋白表达增高，LC3-II/LC3-I比值增高，DRP1和FIS1蛋白表达降低（P<0.05）；与HG+RES组相比，HG+RES+si-SIRT1组 SOD 活力降低，MDA 含量和 ROS 水平升高，细胞相对面积增加，ANF 和 BNP mRNA 表达增加，SIRT1、OPA1、MFN2、BNIP3L蛋白表达降低，LC3-II/LC3-I比值降低，DRP1和FIS1蛋白表达增高（P<0.05）。结论 白藜芦醇可通过减少ROS积累减轻氧化应激损伤抑制高糖诱导的H9c2心肌细胞肥大，其机制可能与促进SIRT1蛋白表达、调节线粒体融合分裂平衡、促进BNIP3L介导的线粒体自噬从而调控线粒体稳态相关。

关键词: 糖尿病心肌病；心肌肥大；白藜芦醇；线粒体；氧化应激；SIRT1

Abstract: Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1 (SIRT1) to maintain mitochondrial homeostasis. Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose (HG) and treated with resveratrol for 72 h. The changes in superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and relative surface of the cells were examined, and the mRNA expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and protein expressions of SIRT1, mitochondrial fusion related proteins optic atrophy protein 1 (OPA1) and mitofusin 2, mitochondrial division related protein dynamin-related protein 1 (DRP1) and fission protein 1 (FIS1), and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting. Results HG exposure significantly decreased SOD activity, increased MDA content, ROS production, relative cell surface, and the mRNA expressions of ANF and BNP in the cardiomyocytes; the protein expressions of SIRT1, OPA1, mitofusin 2 and BNIP3L and LC3-II/LC3-I ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells (P<0.01). All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol (P<0.05). The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1 (P<0.05). Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress, the mechanisms of which involve enhancement of SIRT1 protein expression, regulation of mitochondrial fusion and division balance, and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Key words: diabetic cardiomyopathy; cardiac hypertrophy; resveratrol; mitochondrial; oxidative stress; SIRT1