Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea.
Department of Pathology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Int J Mol Sci. 2020 Feb 21;21(4):1489. doi: 10.3390/ijms21041489.
An increased incidence of myocardial infarction (MI) has recently emerged as the cause of cardiovascular morbidity and mortality worldwide. In this study, cardiac function was investigated in a rat myocardial ischemia/reperfusion (I/R) model using echocardiography. Metformin administration significantly increased ejection fraction and fractional shortening values on Days 3 and 7 when MI occurred, indicating that metformin improved left ventricular systolic function. In the Sham + MET and MI + MET groups, the E' value was significantly different up to Day 3 but not at Day 7. This may mean that left ventricular diastolic function was effectively restored to some extent by Day 7 when metformin was administered. These results suggest that diastolic dysfunction, assessed by echocardiography, does not recover in the early phase of ischemic reperfusion injury in the rat myocardial I/R model. However, administering metformin resulted in recovery in the early phase of ischemic reperfusion injury in this model. Further gene expression profiling of left ventricle tissues revealed that the metformin-treated group had notably attenuated immune and inflammatory profiles. To sum up, a rat myocardial I/R injury model and ultrasound-based assessment of left ventricular systolic and diastolic function can be used in translational research and for the development of new heart failure-related drugs, in addition to evaluating the potential of metformin to improve left ventricular (LV) diastolic function.
心肌梗死(MI)的发病率最近上升,成为全球心血管发病率和死亡率的原因。在这项研究中,使用超声心动图研究了大鼠心肌缺血/再灌注(I/R)模型中的心脏功能。在发生 MI 时,二甲双胍给药在第 3 天和第 7 天显著增加射血分数和分数缩短值,表明二甲双胍改善了左心室收缩功能。在 Sham+MET 和 MI+MET 组中,E'值在第 3 天显著不同,但在第 7 天没有差异。这可能意味着,在给予二甲双胍的第 7 天,左心室舒张功能已在一定程度上得到有效恢复。这些结果表明,在大鼠心肌 I/R 模型缺血再灌注损伤的早期阶段,超声心动图评估的舒张功能并未恢复。然而,在该模型中,给予二甲双胍可恢复缺血再灌注损伤的早期阶段。对左心室组织的进一步基因表达谱分析表明,二甲双胍治疗组的免疫和炎症特征明显减弱。总之,大鼠心肌 I/R 损伤模型和左心室收缩和舒张功能的超声评估可用于转化研究和开发新的心力衰竭相关药物,以及评估二甲双胍改善左心室(LV)舒张功能的潜力。