Li Jinyu, Feng Zikai, Lu Binger, Fang Xinzhe, Huang Danmei, Wang Bin
Institution of Drug Clinical Trial, The Second Affiliated Hospital, Shantou University Medical College, Shantou, 515041, China.
Department of Clinical Pharmacy, Division of Pharmacy, The First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
Biochem Biophys Rep. 2023 Mar 1;34:101444. doi: 10.1016/j.bbrep.2023.101444. eCollection 2023 Jul.
Diabetic cardiomyopathy (DCM) is a common complication of diabetes. DCM causes extensive lesions on cardiac microvasculature that is predominantly cardiac microvascular endothelial cells (CMECs). Reducing high glucose (HG)-induced damage such as oxidative damage and apoptosis could alleviate the development of DCM. The natural polyphenol resveratrol (RSV) is widely suggested as a cardioprotective agent that protect against DCM. However, limited evidence supports the protection of RSV against oxidative damage and apoptosis and study on the direct effects of RSV in CMEC is missing. Therefore, the current paper aimed to illustrate if RSV could attenuate oxidative stress and apoptosis in CMEC and to investigate the underlying mechanisms. Our data showed that HG elevated reactive oxygen species, malondialdehyde, decreased superoxide dismutase activity, increased apoptotic cell percentage in CMEC, which were reversed by RSV administration. In addition, RSV demonstrated antioxidative and anti-apoptotic effects in CMEC through AMPK/Sirt1 activation, further confirmed by AMPK inhibition or Sirt1 silencing. This study provides new evidence to support RSV as a potential cardioprotective alternative in treating DCM.
糖尿病性心肌病(DCM)是糖尿病常见的并发症。DCM会导致心脏微血管出现广泛病变,而心脏微血管主要由心脏微血管内皮细胞(CMECs)组成。减少高糖(HG)诱导的损伤,如氧化损伤和细胞凋亡,可缓解DCM的发展。天然多酚白藜芦醇(RSV)被广泛认为是一种预防DCM的心脏保护剂。然而,支持RSV预防氧化损伤和细胞凋亡的证据有限,且缺乏关于RSV对CMEC直接作用的研究。因此,本文旨在阐明RSV是否能减轻CMEC中的氧化应激和细胞凋亡,并探究其潜在机制。我们的数据表明,HG会增加活性氧、丙二醛,降低超氧化物歧化酶活性,增加CMEC中的凋亡细胞百分比,而RSV给药可逆转这些变化。此外,RSV通过激活AMPK/Sirt1在CMEC中发挥抗氧化和抗凋亡作用,AMPK抑制或Sirt1沉默进一步证实了这一点。本研究为支持RSV作为治疗DCM的潜在心脏保护替代药物提供了新证据。