Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, 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 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
Biochem Pharmacol. 2020 Dec;182:114295. doi: 10.1016/j.bcp.2020.114295. Epub 2020 Oct 17.
An increase in the number of fragmented mitochondria contributes to the pathogenesis of ischemia-reperfusion (I/R) injury. Also, mitochondrial fission has shown an increase in obese condition. However, the cardioprotective roles of a mitochondrial fission inhibitor in obesity with cardiac I/R injury are unclear. We hypothesized that a fission inhibitor (Mdivi-1) reduces cardiac dysfunction during I/R injury in pre-diabetic rats. Male Wistar rats (n = 40) were received a high-fat diet for 12 weeks to induce prediabetes. Then, rats underwent a 30-min coronary artery ligation was performed followed by reperfusion for 120 min. These I/R rats were given either: (1) vehicle or Mdivi-1 treatment at 3 time points relative to onset of ischemia: (2) pre-ischemia; (3) during ischemia; and (4) at onset of reperfusion. Cardiac function, myocardial infarct size, mitochondrial function and dynamic balance were determined. Interestingly, Mdivi-1 given at any time points effectively attenuated mitochondrial reactive oxygen species production, depolarization, swelling, and dynamic imbalance, resulting in reduced arrhythmias, myocardial cell death, infarct size and enhanced cardiac performance during I/R injury in pre-diabetic rats. Taken together, inhibition of mitochondrial fission effectively protected the heart against cardiac I/R injury regardless of the time of administration in pre-diabetic rats.
线粒体碎片化数量的增加导致了缺血再灌注（I/R）损伤的发病机制。此外，在肥胖情况下也观察到线粒体分裂增加。然而，线粒体分裂抑制剂在肥胖合并心肌 I/R 损伤中的心脏保护作用尚不清楚。我们假设，线粒体分裂抑制剂（Mdivi-1）可减少糖尿病前期大鼠的 I/R 损伤期间的心脏功能障碍。雄性 Wistar 大鼠（n=40）接受高脂肪饮食 12 周以诱导糖尿病前期。然后，大鼠进行 30 分钟的冠状动脉结扎，然后再灌注 120 分钟。这些 I/R 大鼠分别给予：（1）载体或 Mdivi-1 治疗，相对于缺血开始时间有 3 个时间点：（2）缺血前；（3）缺血期间；和（4）再灌注开始时。测定心脏功能、心肌梗死面积、线粒体功能和动态平衡。有趣的是，Mdivi-1 在任何时间点给药均可有效减轻线粒体活性氧的产生、去极化、肿胀和动态失衡，从而减少心律失常、心肌细胞死亡、梗死面积，并在糖尿病前期大鼠的 I/R 损伤期间增强心脏功能。总之，无论在糖尿病前期大鼠中给药时间如何，抑制线粒体分裂都能有效地保护心脏免受心肌 I/R 损伤。
