Wang X, Yu F, Zheng W-Q
Department of Pharmacy, Weihai Central Hospital, Weihai, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):294-303. doi: 10.26355/eurrev_201908_18660.
To clarify the role of aldose reductase inhibitor (ARI) in the high glucose-induced cardiomyocyte apoptosis and its mechanism.
In this study, H9c2 cardiomyocytes were employed as objects, high-glucose medium as stimulus, and ARI Epalrestat as a therapeutic drug. The cell apoptosis and activity changes of nitric oxide synthase (NOS), NO, and reactive oxygen species (ROS) were evaluated via Hoechst staining, enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and Western blotting. In addition, the mitochondrial membrane potential was measured via fluorescence counting.
Epalrestat inhibited the activity of AR to improve high glucose-induced oxidative stress in cardiomyocytes, weaken ROS activity, relieve the inhibition on NO activity, alleviate mitochondrial membrane potential damage, reduce the level of high glucose-induced cardiomyocyte apoptosis, and suppress the expression and activity of Caspase-3, thereby preventing high glucose-induced cardiomyocyte apoptosis.
ARI protects against high glucose-induced cardiomyocyte apoptosis.
阐明醛糖还原酶抑制剂（ARI）在高糖诱导的心肌细胞凋亡中的作用及其机制。
本研究以H9c2心肌细胞为研究对象，高糖培养基为刺激因素，ARI依帕司他为治疗药物。通过Hoechst染色、酶联免疫吸附测定（ELISA）、聚合酶链反应（PCR）和蛋白质免疫印迹法评估细胞凋亡以及一氧化氮合酶（NOS）、一氧化氮（NO）和活性氧（ROS）的活性变化。此外，通过荧光计数测量线粒体膜电位。
依帕司他抑制醛糖还原酶（AR）的活性，改善高糖诱导的心肌细胞氧化应激，减弱ROS活性，减轻对NO活性的抑制，减轻线粒体膜电位损伤，降低高糖诱导的心肌细胞凋亡水平，并抑制半胱天冬酶-3（Caspase-3）的表达和活性，从而防止高糖诱导的心肌细胞凋亡。
ARI可保护心肌细胞免受高糖诱导的凋亡。
