Yao Hong, Han Xiangyang, Han Xiuzhen
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, 250012, Shandong, China.
Am J Cardiovasc Drugs. 2014 Dec;14(6):433-42. doi: 10.1007/s40256-014-0089-9.
Apoptosis occurs frequently in myocardial infarction, oxidative stress injury, and ischemia/reperfusion injury, and plays a pivotal role in the development of heart diseases. Inhibition of apoptosis alone does not necessarily lead to meaningful rescue in terms of either cardiomyocyte survival or function. Activation of the PI3K/Akt signaling pathway induced by insulin not only inhibits cardiomyocyte apoptosis but also substantially preserves and even improves regional and overall cardiac function. Insulin can protect cardiomyocytes from apoptosis by regulating a number of signaling molecules, such as eNOS, FOXOs, Bad, GSK-3β, mTOR, NDRG2, and Nrf2, through activating PI3K and Akt. This review focuses on the protective mechanisms and targets of insulin identified in the prevention and treatment of myocardial injury.
细胞凋亡频繁发生于心肌梗死、氧化应激损伤及缺血/再灌注损伤中,并在心脏病的发展过程中起关键作用。仅抑制细胞凋亡不一定能在心肌细胞存活或功能方面带来有意义的挽救效果。胰岛素诱导的PI3K/Akt信号通路激活不仅能抑制心肌细胞凋亡,还能显著维持甚至改善局部和整体心脏功能。胰岛素可通过激活PI3K和Akt,调节多种信号分子,如内皮型一氧化氮合酶(eNOS)、叉头框蛋白O(FOXOs)、促凋亡蛋白Bad、糖原合成酶激酶-3β(GSK-3β)、哺乳动物雷帕霉素靶蛋白(mTOR)、N-myc下游调节基因2(NDRG2)和核因子E2相关因子2(Nrf2),从而保护心肌细胞免于凋亡。本综述聚焦于胰岛素在预防和治疗心肌损伤中所确定的保护机制及靶点。