Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Department of Cardiovascular Surgery, Fukuyama City Hospital, Fukuyama, Hiroshima, 721-8511, Japan.
Sci Rep. 2024 Jul 16;14(1):16337. doi: 10.1038/s41598-024-67195-3.
It has been suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardioprotective effects during myocardial ischemia/reperfusion (I/R) independent of glucose-lowering action. However, the effects of SGLT2 inhibitors on structural damage to cardiomyocytes in the ischemic region during I/R remain unknown. We applied a microdialysis technique to the heart of anesthetized rats and investigated the effects of an SGLT2 inhibitor, dapagliflozin, on myocardial interstitial myoglobin levels in the ischemic region during coronary occlusion followed by reperfusion. Dapagliflozin was administered systemically (40 μg/body iv) or locally via a dialysis probe (100 μM and 1 mM) 30 min before coronary occlusion. In the vehicle group, coronary occlusion increased the dialysate myoglobin concentration in the ischemic region. Reperfusion further increased the dialysate myoglobin concentration. Intravenous administration of dapagliflozin reduced dialysate myoglobin concentration during ischemia and at 0-15 min after reperfusion, but local administration (100 μM and 1 mM) did not. Therefore, acute systemic administration of dapagliflozin prior to ischemia has cardioprotective effects on structural damage during I/R.
有人提出，钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂在心肌缺血/再灌注（I/R）期间具有独立于降血糖作用的心脏保护作用。然而，SGLT2 抑制剂对 I/R 期间缺血区域心肌细胞结构损伤的影响尚不清楚。我们应用微透析技术研究了 SGLT2 抑制剂达格列净在冠状动脉闭塞后继发再灌注期间对缺血区心肌间质肌红蛋白水平的影响。在冠状动脉闭塞前 30 分钟，达格列净通过全身给药（40μg/体重静脉内）或通过透析探头局部给药（100μM 和 1mM）。在载体组中，冠状动脉闭塞增加了缺血区的透析液肌红蛋白浓度。再灌注进一步增加了透析液肌红蛋白浓度。静脉内给予达格列净可降低缺血期间和再灌注后 0-15 分钟的透析液肌红蛋白浓度，但局部给药（100μM 和 1mM）则没有。因此，在缺血前急性给予达格列净可对 I/R 期间的结构损伤产生心脏保护作用。
