Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, England, United Kingdom.
Biomed Pharmacother. 2020 Oct;130:110604. doi: 10.1016/j.biopha.2020.110604. Epub 2020 Aug 7.
Cardiac ischemia/reperfusion (I/R) injury following reperfusion therapy in acute myocardial infarction results in mitochondrial dynamic imbalance and cardiomyocyte apoptosis. Although diabetic patients taking metformin have been shown to have a lower risk of myocardial infarction, the efficacy of the cardioprotection conferred by metformin regarding the mitochondrial function and dynamic in cardiac I/R injury are still inconclusive. In addition, the comparative effects between different doses of metformin given acutely prior to cardiac I/R injury have never been investigated. Fifty 8-week-old male Wistar rats weighing 300-350 g were divided into sham-operated (n = 10) and cardiac I/R-operated (n = 40) groups. In the cardiac I/R group, rats underwent 30-min ischemia followed by 120-min reperfusion and were randomly divided into four subgroups (n = 10/group): control (received normal saline), metformin (100, 200, and 400 mg/kg). The arrhythmia score, cardiac function, infarct size, mortality rate, mitochondrial function and apoptosis, were determined. Metformin (200 mg/kg) exerted the highest level of cardioprotection through reduction in arrhythmia, infarct size, mitochondrial fission, and apoptosis, in addition to preservation of mitochondrial function, leading to the attenuation of cardiac dysfunction. Doses of metformin (100 and 400 mg/kg) also improved mitochondrial and cardiac function, but to a lesser extent than metformin (200 mg/kg). In conclusion, metformin exerts cardioprotection by attenuating mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. These led to decreased infarct size and eventual improvement in cardiac function in rats with acute cardiac I/R injury. These findings indicate the potential clinical benefits of acute metformin treatment in acute myocardial infarction.
心肌缺血/再灌注（I/R）损伤是急性心肌梗死后再灌注治疗的结果，导致线粒体动态失衡和心肌细胞凋亡。尽管接受二甲双胍治疗的糖尿病患者发生心肌梗死的风险较低，但二甲双胍对心肌 I/R 损伤中线粒体功能和动态的保护作用仍不确定。此外，从未研究过在心肌 I/R 损伤前给予不同剂量的二甲双胍的比较效果。
将 50 只 8 周龄雄性 Wistar 大鼠（体重 300-350g）分为假手术（n=10）和心脏 I/R 手术（n=40）组。在心脏 I/R 组中，大鼠经历 30 分钟缺血，然后再灌注 120 分钟，并随机分为四组（n=10/组）：对照组（给予生理盐水），二甲双胍（100、200 和 400mg/kg）。测定心律失常评分、心功能、梗死面积、死亡率、线粒体功能和凋亡。
二甲双胍（200mg/kg）通过减少心律失常、梗死面积、线粒体分裂和凋亡，以及保护线粒体功能，减轻心脏功能障碍，发挥最高水平的心脏保护作用。二甲双胍（100 和 400mg/kg）剂量也改善了线粒体和心脏功能，但程度低于二甲双胍（200mg/kg）。
总之，二甲双胍通过减轻线粒体功能障碍、线粒体动态失衡和细胞凋亡发挥心脏保护作用。这些导致了急性心肌 I/R 损伤大鼠梗死面积的减少，最终改善了心脏功能。这些发现表明急性二甲双胍治疗在急性心肌梗死中的潜在临床益处。
