Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China; Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, Jiangsu, China.
Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
Eur J Pharm Sci. 2021 Jun 1;161:105788. doi: 10.1016/j.ejps.2021.105788. Epub 2021 Mar 6.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been confirmed to reduce the rate of rehospitalization for heart failure and cardiovascular death in diabetic patients. The aim of our study was to investigate the cardioprotective role of SGLT2 inhibitors in early myocardial infarction (MI) of non-diabetic mice.
C57BL/6 mice underwent left artery coronary artery descending (LAD) ligation to induce MI. Following the surgery, animals were randomized to receive saline or empagliflozin. Empagliflozin (EMPA) was administrated at 10 mg/kg per day by oral gavage for 2 weeks. Echocardiography, histological staining and qualitative RT-PCR were performed to assess the cardiac remodeling post MI. In vitro experiments were performed to evaluate the effect of empagliflozin on apoptosis, oxidative stress and mitochondrial membrane potential of cardiomyocyte subjected to hypoxic treatment.
Compared with MI group, the empagliflozin treatment group showed improved cardiac function, reduced infarct size and interstitial fibrosis. Empagliflozin also inhibited cardiomyocyte apoptosis by alleviating oxidative stress and restoring mitochondrial membrane potential. Immunoblotting analysis revealed activated AMP-activated protein kinase (AMPK) signaling may mediated the cardioprotective role of empagliflozin.
In summary, empagliflozin could inhibit cardiomyocyte apoptosis and improve cardiac remodeling early MI, which provided insights into the benefic effect of empagliflozin on MI patients without diabetes.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂已被证实可降低糖尿病患者心力衰竭和心血管死亡的再住院率。我们的研究目的是探讨 SGLT2 抑制剂在非糖尿病小鼠早期心肌梗死（MI）中的心脏保护作用。
C57BL/6 小鼠进行左冠状动脉下（LAD）结扎以诱导 MI。手术后，动物随机接受生理盐水或恩格列净。恩格列净（EMPA）以 10mg/kg/天的剂量通过口服灌胃给药 2 周。进行超声心动图、组织学染色和定性 RT-PCR 以评估 MI 后心脏重构。进行体外实验以评估恩格列净对缺氧处理的心肌细胞凋亡、氧化应激和线粒体膜电位的影响。
与 MI 组相比，恩格列净治疗组显示出改善的心脏功能、减小的梗死面积和间质纤维化。恩格列净还通过减轻氧化应激和恢复线粒体膜电位来抑制心肌细胞凋亡。免疫印迹分析显示，激活的 AMP 激活的蛋白激酶（AMPK）信号通路可能介导了恩格列净的心脏保护作用。
总之，恩格列净可抑制心肌细胞凋亡并改善早期 MI 中的心脏重构，这为恩格列净对无糖尿病 MI 患者的有益作用提供了新的见解。
