Gong Lei, Wang Xuyang, Pan Jinyu, Zhang Mingjun, Liu Dian, Liu Ming, Li Li, An Fengshuang
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 WenHuaXi Road, Jinan, Shandong 250012, China.
The Second Affiliated Hospital of Xuzhou Medical University, No.32 MeiJian Road, Quanshan District, Xuzhou, Jiangsu 221000, China.
Open Med (Wars). 2020 Dec 11;15(1):47-57. doi: 10.1515/med-2021-0005. eCollection 2021.
The purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism.
Sprague-Dawley (SD) rats ( = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion.
pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+d/d ), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (-d/d ) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells.
The combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.
本研究旨在评估瑞舒伐他汀（RSV）与达格列净（DGZ）预处理联合治疗在心肌缺血/再灌注（I/R）损伤中的作用，并进一步探究其潜在机制。
将25只Sprague-Dawley（SD）大鼠随机分为五组：（1）假手术组；（2）I/R组；（3）I/R + RSV（10mg/kg）组；（4）I/R + DGZ（1mg/kg）组；（5）I/R + RSV（10mg/kg）+ DGZ（1mg/kg）组。通过左前降支闭塞30分钟，随后再灌注120分钟诱导I/R模型。
与I/R组相比，RSV和DGZ预处理分别显著减小梗死面积，显著提高左心室收缩压水平、左心室压力最大上升速率（+d/d ），降低左心室舒张末期压力（LVEDP）水平、左心室压力最大下降速率（-d/d ）以及肌酸激酶（CK）、肌酸激酶同工酶MB（CK-MB）和心肌肌钙蛋白I等心肌酶活性。H9C2细胞暴露于缺氧/复氧环境以模拟I/R模型。给予25μM RSV和50μM DGZ显著增强细胞活力，上调p-PI3K、p-Akt、p-mTOR和Bcl-2的表达水平，而下调裂解的半胱天冬酶3、Bax。TUNEL检测表明，RSV和DGZ预处理可减少H9C2细胞凋亡。
与单独使用RSV或DGZ相比，RSV与DGZ联合使用显著增强心脏保护作用。RSV和DGZ通过激活PI3K/AKt/mTOR信号通路对I/R损伤具有潜在的心脏保护作用。
