| 白 净,徐 晶,杨禹娟,王亚萍,李文波.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[J].,2021,(22):4223-4228 |
| 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 |
| 投稿时间：2021-04-04 修订日期：2021-04-28 |
| DOI：10.13241/j.cnki.pmb.2021.22.005 |
| 中文关键词: 达格列净 心肌缺血 糖尿病 血液动力学 线粒体 |
| 英文关键词: Dapagliflozin Myocardial ischemia Diabetes Hemodynamics Mitochondria |
| 基金项目: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） |
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| 中文摘要: |
| 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）。心肌缺血组较对照组PGC1-α和CPT-1的mRNA表达降低（P<0.05），达格列净组较心肌缺血组PGC1-α和CPT-1的mRNA表达升高（P<0.05）。结论：达格列净给药可减糖尿病合并心肌缺血大鼠的心肌梗死面积，增强心室功能和心肌细胞能量代谢，发挥心脏保护作用。 |
| 英文摘要: |
| ABSTRACT 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-α and 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<0.05). Compared with the control group, the number of TUNEL positive cells in the myocardial ischemia group increased(P<0.05). In addition, compared with the myocardial ischemia group, the number of TUNEL positive cells in the dapagliflozin group was reduced(P<0.05). Mitochondrial membrane potential MMP. Compared with the control group, the ATP content and MMP of the myocardial ischemia group were lower (P<0.05), and the ADP/ATP ratio was increased (P<0.05). The ATP content and MMP of the dapagliflozin group were higher than the myocardial ischemia group (P<0.05), the ADP/ATP ratio decreased(P<0.05). Compared with the control group, the protein expression of MFN2 and OPA1 was lower in the myocardial ischemia group(P<0.05), and the protein expression of DRP1 was increased(P<0.05). The protein expression of MFN2 and OPA1 in the dapagliflozin group was higher than that in the myocardial ischemia group (P<0.05), the expression of DRP1 protein decreased (P<0.05). The mRNA expression of PGC1-α and CPT-1 in the myocardial ischemia group was lower than that in the control group(P<0.05), and the mRNA expression of PGC1-α and CPT-1 in the dapagliflozin group was higher than that in the myocardial ischemia group(P<0.05). Conclusion: Dapagliflozin administration can reduce the myocardial infarction area in diabetic rats with myocardial ischemia, enhance ventricular function and myocardial cell energy metabolism, and play a cardioprotective effect. |
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