达格列净对糖尿病合并心肌缺血大鼠心肌细胞能量代谢及血液流变学的作用研究  

Effects of Dapagliflozin on Energy Metabolism and Hemorheology of Myocardial Cells in Diabetic Rats with Myocardial Ischemia

作　　者：白净[1] 徐晶[2] 杨禹娟[1] 王亚萍[1] 李文波[1] BAI Jing;XU Jing;YANG Yu-juan;WANG Ya-ping;LI Wen-bo(Department of Cardiovascular Medicine III,Shaanxi Provincial People's Hospital,Xi'an,Shaanxi,710068,China;Department of Cardiovascular Medicine I,Shaanxi Provincial People's Hospital,Xi'an,Shaanxi,710068,China)

机构地区：[1]陕西省人民医院心血管内三科,陕西西安710068 [2]陕西省人民医院心血管内一科,陕西西安710068

出　　处：《现代生物医学进展》2021年第22期4223-4228,共6页Progress in Modern Biomedicine

基　　金：陕西省自然科学基础研究计划项目(2019JM-530);陕西省分子心脏病学重点实验室开放课题基金项目(KLMC-2018-04)。

摘　　要：目的:探讨达格列净对糖尿病合并心肌缺血大鼠心肌细胞能量代谢及血液流变学的作用研究。方法:2型糖尿病雌性Goto-Kakizaki大鼠根据实验要求分为三组:对照组,心肌缺血组和达格列净组。通过右颈总动脉血流动力学系统评估大鼠SBP、MAP和DBP;LabScribe 2软件操作的记录系统监测大鼠的心脏收缩舒张功能;TTC染色和组织学分别检测大鼠的心肌梗塞面积百分比和心肌损伤评分;TUNEL测定法测定大鼠心肌细胞凋亡;测定试剂盒和荧光追踪检测大鼠心肌中的ATP含量、ADP/ATP比率、线粒体膜电位MMP;蛋白印迹分析线粒体裂解融合因子线粒体蛋白2(Mitochondrial protein 2,MFN2),视神经萎缩1(Optic nerve atrophy 1,OPA1)和动力蛋白相关的蛋白1(Dynein-related protein 1,DRP1)的蛋白表达;RT-PCR分析大鼠心肌细胞中能量代谢相关因子PGC1-α和CPT-1的转录。结果:心肌缺血组较对照组的SBP、MAP升高(P<0.05),达格列净组较心肌缺血组降低(P<0.05),与对照组相比,心肌缺血组和达格列净组的DBP比较无差异(P>0.05)。心肌缺血组较对照组LVEF降低(P<0.05),LVIDs、LVPWs和LVPWd升高(P<0.05),达格列净组较心肌缺血组的LVEF升高(P<0.05),LVIDs、LVPWs和LVPWd降低(P<0.05)。心肌缺血组较对照组的梗塞面积占比和组织损伤评分升高(P<0.05),达格列净组较心肌缺血组梗塞面积、组织损伤评分降低(P<0.05)。与对照组相比,心肌缺血组TUNEL阳性细胞数量增多(P<0.05)。此外,与心肌缺血组相比,达格列净组的TUNEL阳性细胞数量降低(P<0.05)。线粒体膜电位MMP。心肌缺血组较对照组的ATP含量和MMP降低(P<0.05),ADP/ATP比率升高(P<0.05),达格列净组较心肌缺血组ATP含量和MMP升高(P<0.05),ADP/ATP比率降低(P<0.05)。心肌缺血组较对照组MFN2和OPA1的蛋白表达降低(P<0.05),DRP1蛋白表达升高(P<0.05),达格列净组较心肌缺血组MFN2和OPA1的蛋白表达升高(P<0.05),DRP1蛋白表达降低(P<0.05)。心肌缺Objective:To investigate the effect of dapagliflozin on myocardial cell energy metabolism and hemorheology in diabetic rats with myocardial ischemia.Methods:Female Goto-Kakizaki rats with type 2 diabetes were divided into three groups according to experimental requirements:control group,myocardial ischemia group and dapagliflozin group.The rat SBP,MAP and DBP were evaluated by the right common carotid artery hemodynamic system.The systolic and diastolic function of rats were monitored by a recording system operated by LabScribe 2 software.The percentage of myocardial infarction area and myocardial injury score were detected by TTC staining and histology.The apoptosis of rat cardiomyocytes was measured by TUNEL assay.Detect the ATP content,ADP/ATP ratio,mitochondrial membrane potential MMP in rat myocardium by measuring kit and fluorescence tracking.The protein expressions of mitochondrial cleavage fusion factor mitochondrial protein 2(Mitochondrial protein 2,MFN2),optic nerve atrophy 1(OPA1)and Dynein-related protein 1(DRP1)were analyzed by western blot.The transcription of energy metabolism-related factors PGC1-αand CPT-1 in rat cardiomyocytes was analyzed by RT-PCR.Results:Compared with the control group,the SBP and MAP of the myocardial ischemia group were increased(P<0.05),and the dapagliflozin group was lower than the myocardial ischemia group(P<0.05).Compared with the control group,the myocardial ischemia group There was no difference in the DBP of the gliflozin group(P>0.05).Compared with the control group,the LVEF of the myocardial ischemia group was lower(P<0.05),and the LVIDs,LVPWs and LVPWd were increased(P<0.05).The LVEF of the dapagliflozin group was higher than that of the myocardial ischemia group(P<0.05).LVIDs,LVPWs and LVPWd decreased(P<0.05).Compared with the control group,the infarct area and tissue damage score of the myocardial ischemia group were higher(P<0.05),and the infarct area and tissue damage score of the dapagliflozin group were lower than that of the myocardial ischemia group(P<0.0

关 键 词：达格列净 心肌缺血 糖尿病 血液动力学 线粒体 

分 类 号：R-33[医药卫生] R587.2