Song C, Huang Z, Chen W, Wang F, Cai L, Zhao F, Zhao Y
Department of Geriatrics, Xiehe Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen 518000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2013 Jul 20;43(7):1136-1144. doi: 10.12122/j.issn.1673-4254.2023.07.10.
To evaluate the effect of empagliflozin (EMPA) in mitigating microvascular and endothelial damage induced by myocardial ischemia-reperfusion (I/R) injury.
Fifteen male C57BL/6J mice were randomized into shamoperated group, I/R group and I/R+EMPA group, and in the latter two groups, myocardial I/R injury was induced by ligating the left anterior descending coronary artery followed by reperfusion for 2 h. EMPA treatment was administered at the daily dose of 10 mg/kg for 7 days. After the treatment, the changes in myocardial microvascular structure of the mice were observed under electron microscopy. In the cell experiment, cultured human coronary artery endothelial cells (HCAECs) were treated with 10 μmol/L EMPA before exposure to hypoxia for 45 min followed normoxic culture for 2 h. Western blotting and immunofluorescence assay were performed to observe fibrin accumulation and endothelial cell protein expressions in the myocardial tissues of the mice and in HCAECs, and RT-qPCR was used to detect the expressions of pro-inflammatory cytokines.
Electron microscopy revealed significant myocardial microvascular wall thickening and lumen narrowing in mice with myocardial I/R injury. Fibrin accumulation and ICAM1 expression in the microvessels were more pronounced in I/R group than in the sham-operated and I/R + EMPA groups ( < 0.05). EMPA treatment obviously alleviated microvascular occlusion and microthrombus formation induced by I/R injury. At the cellular level, the protein levels of p-eNOS, Fak, and Src kinases in hypoxic exposure group were significantly lower than those in the control and EMPA treatment groups ( < 0.05). Hypoxic exposure significantly reduced mitochondrial DNA replication and transcription and lowered the expression levels of Cox-Ⅰ and Cox-Ⅱ in HCAECs, and these changes were obviously improved by EMPA treatment ( < 0.05).
EMPA can alleviate myocardial I/R injury by maintaining mitochondrial homeostasis to protect the microvascular system.
评估恩格列净（EMPA）减轻心肌缺血再灌注（I/R）损伤所致微血管和内皮损伤的作用。
将15只雄性C57BL/6J小鼠随机分为假手术组、I/R组和I/R+EMPA组，后两组通过结扎左冠状动脉前降支再灌注2小时诱导心肌I/R损伤。EMPA按每日10mg/kg的剂量给药，共7天。治疗后，在电子显微镜下观察小鼠心肌微血管结构的变化。在细胞实验中，培养的人冠状动脉内皮细胞（HCAECs）在缺氧45分钟前用10μmol/L的EMPA处理，随后进行常氧培养2小时。采用蛋白质免疫印迹法和免疫荧光分析法观察小鼠心肌组织和HCAECs中纤维蛋白积聚和内皮细胞蛋白表达情况，并用RT-qPCR检测促炎细胞因子的表达。
电子显微镜显示，心肌I/R损伤小鼠的心肌微血管壁明显增厚，管腔狭窄。I/R组微血管中纤维蛋白积聚和ICAM1表达比假手术组和I/R+EMPA组更明显（P<0.05）。EMPA治疗明显减轻了I/R损伤诱导的微血管闭塞和微血栓形成。在细胞水平上，缺氧暴露组中p-eNOS、Fak和Src激酶的蛋白水平明显低于对照组和EMPA治疗组（P<0.05）。缺氧暴露显著降低了HCAECs中线粒体DNA的复制和转录，并降低了Cox-Ⅰ和Cox-Ⅱ的表达水平，而EMPA治疗明显改善了这些变化（P<0.05）。
EMPA可通过维持线粒体稳态来保护微血管系统，从而减轻心肌I/R损伤。
