Ideishi Akihito, Suematsu Yasunori, Tashiro Kohei, Morita Hidetaka, Kuwano Takashi, Tomita Sayo, Nakai Kanji, Miura Shin-Ichiro
Department of Cardiology, Fukuoka University School of Medicine, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, Japan.
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.
Cardiol Res. 2021 Apr;12(2):91-97. doi: 10.14740/cr1194. Epub 2021 Jan 24.
Sodium-glucose co-transporter 2 inhibitor (SGLT2i) and dipeptidyl peptidase 4 inhibitor (DPP4i) are oral hypoglycemic agents. Although SGLT2i has been shown having the beneficial effects on heart failure in basic and clinical studies, the combined effects of SGLT2i and DPP4i have not been established well. We investigated the effects of SGLT2i and DPP4i against diabetes mice model of myocardial ischemia-reperfusion injury.
Streptozotocin-induced diabetic C57BL/6J mice were divided into control (vehicle), empagliflozin (30 mg/kg/day), linagliptin (3 mg/kg/day) and combination (30 mg/kg/day and 3 mg/kg/day, respectively) groups. After 7 days of drug administration, 30 min of myocardial ischemia was performed. We investigated body weight, heart weight, blood glucose, and cardiac functions by pressure-volume Millar catheter followed by 28 days of additional drug administration.
Blood glucose levels, body weight, and heart weight were not significantly different between the groups. In Millar catheter analysis, left ventricular volume at the peak left ventricular ejection rate which is one of the cardiac systolic parameters in combination group was significantly preserved than that in control (P = 0.036). The cardiac index in the combination group tended to be preserved compared to that in the control (P = 0.06). The pathological fibrotic area in the left ventricle in the combination group also tended to be smaller (P = 0.08).
Combination therapy with linagliptin and empagliflozin preserved cardiac systolic function on the diabetes mice model of myocardial ischemia-reperfusion injury independent of blood glucose levels.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）和二肽基肽酶4抑制剂（DPP4i）是口服降糖药。尽管在基础和临床研究中已表明SGLT2i对心力衰竭有有益作用，但SGLT2i和DPP4i的联合作用尚未得到充分证实。我们研究了SGLT2i和DPP4i对糖尿病小鼠心肌缺血-再灌注损伤模型的影响。
将链脲佐菌素诱导的糖尿病C57BL/6J小鼠分为对照组（溶媒）、恩格列净组（30毫克/千克/天）、利格列汀组（3毫克/千克/天）和联合治疗组（分别为30毫克/千克/天和3毫克/千克/天）。给药7天后，进行30分钟的心肌缺血。通过压力-容积米勒导管研究体重、心脏重量、血糖和心脏功能，随后再给药28天。
各组之间的血糖水平、体重和心脏重量无显著差异。在米勒导管分析中，联合治疗组作为心脏收缩参数之一的左心室射血率峰值时的左心室容积明显比对照组保留得更好（P = 0.036）。联合治疗组的心脏指数与对照组相比有保留的趋势（P = 0.06）。联合治疗组左心室的病理纤维化面积也有变小的趋势（P = 0.08）。
在糖尿病小鼠心肌缺血-再灌注损伤模型中，利格列汀和恩格列净联合治疗可保留心脏收缩功能，且与血糖水平无关。
