SIRT1是一种高度保守的烟酰胺腺嘌呤二核苷酸(NAD+)依赖性组蛋白脱乙酰酶。它参与各种病理生理过程的调节,包括细胞增殖,生存,分化,自噬,和氧化应激。SIRT1的治疗性激活保护心脏和心肌细胞免受病理相关应激,特别是心肌缺血/再灌注(I/R)。自噬是能量或营养缺乏时细胞存活的重要代谢途径,缺氧,或氧化应激。自噬是心肌I/R损伤的一把双刃剑。在缺血阶段激活自噬可以清除多余的代谢废物,并有助于确保心肌细胞存活。而再灌注过程中过度的自噬会消耗细胞成分并导致自噬性细胞死亡。越来越多的I/R损伤研究表明,SIRT1参与自噬过程并调节心肌I/R。SIRT1通过多种途径调节自噬,例如FOXOs的去乙酰化,ATGs,LC3近年来研究证实,SIRT1介导的自噬在心肌I/R损伤的不同阶段发挥着不同的作用。通过在I/R损伤的不同阶段靶向SIRT1介导的自噬机制,新的小分子药物,miRNA激活剂,或者可以开发阻滞剂。例如,白藜芦醇,七氟醚,槲皮素,缺血阶段的褪黑激素,黄连碱,姜黄素,小檗碱,再灌注过程中的一些miRNA,参与调节SIRT1-自噬轴,发挥心脏保护作用。这里,我们总结了SIRT1调控自噬在心肌I/R损伤中的可能机制以及相关的分子药物应用,以确定治疗心肌I/R损伤的策略。
SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.