达格列净预处理对糖尿病大鼠心肌缺血再灌注损伤的影响

Effects of Dapagliflozin Preconditioning on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

目的:研究达格列净预处理对糖尿病大鼠心肌缺血—再灌注(I-R)损伤的影响,并对其作用机制进行探讨。方法:选择糖尿病大鼠作为样本,对模型进行构建,本次实验共使用雄性SD大鼠24只,把其平均分为三组(n=8),第1组为假手术组,第2组为达格列净组,第3组为I-R组。假手术组样本在给予其开胸处理之后不进行结扎操作,无其他药物处理。达格列净组在结扎左前降支(LAD)前连续口服达格列净,给药30d(1次/d,1mg/kg),第31天结扎LAD 30min,再灌注2h。I-R组结扎LAD 30min,再灌注2h,无其他药物处理。连续监测肢体Ⅱ导联心电图,观察心率及ST段改变,再灌注2h末抽血查血清磷酸肌酸激酶同工酶(CK-MB)与乳酸脱氢酶(LDH),用伊文斯蓝(Evans blue)及三苯氯化四氮唑(TTC)双重染色方法测定心肌梗死及缺血面积,采用TUNEL法测心肌细胞凋亡指数(AI)。结果:与I-R组相比,达格列净组可减少CK-MB与LDH的释放(P<0.05),减少心梗面积与细胞AI(P<0.05);与假手术组相比,达格列净组与I-R组CK-MB与LDH的释放明显增加(P<0.05),心梗面积与细胞AI也明显增加(P<0.05)。结论:达格列净预处理可减少心梗面积与细胞AI,减少CK-MB与LDH的释放,起到对I-R心肌的保护作用。

Objective:To study and analyze the effects of dapagliflozin preconditioning on myocardial ischemia-reperfusion injury in diabetic rats,and further explore its mechanism.Methods:Diabetes rats were selected as samples to construct the model.In this experiment,24 male SD rats were used and divided into three groups on average(n=8),the first group is the sham-operated group,the second group is the Dapagliflozin group,and the third group is the I-R group.Sham-operated group samples were not subjected to ligation after undergoing thoracotomy,without other medicine preconditioning.Dapagliflozin group was orally administered for 30 days(once a day,1mg/kg)before LAD ligation,followed by 30 minutes of LAD ligation and 2 hours of reperfusion on the 31st day.I-R group underwent LAD ligation for 30 minutes and reperfusion for 2 hours without any other medicine preconditioning.Monitor the changes of heart rate and ST-stage by ECG leadⅡ.The levels of CK-MB and LDH were measured 2 hours after reperfusion.Myocardial infarction(MI)size and risk size were determined by Evans blue and TTC staining.Myocardial cell apoptotic index was determined by TUNEL.Results:Compared with I-R group,Dapagliflozin group decrease the releasing of CK-MB and LDH,decrease MI side and apoptotic index.Compared with sham-operated group,Dapagliflozin group and I-R group increased significantly the releasing of CK-MB and LDH,increased significantly MI side and apoptotic index(P<0.05).Conclusion:Dapagliflozin preconditioning protects the myocardium against I-R injury by decreasing MI side and apoptotic index,and decreasing the releasing of CK-MB and LDH.