论文部分内容阅读
目的研究腺苷A1受体部分型激动剂VCP28对1型糖尿病大鼠心肌缺血/再灌注损伤的保护作用,并探讨其机制。方法建立1型糖尿病SD大鼠离体心脏缺血/再灌注模型,按照假手术组(Sham组)、单纯缺血/再灌注组(I/R组)和I/R+VCP28(腺苷A1受体部分型激动剂)组进行实验(n=8)。实验过程中持续描记采集左室压(LVP),根据压力波形分析左室发展压(LVDP)和最大收缩/舒张速率(±dp/dt_(max));TTC染色法测定心肌梗死面积;Western Blot法检测各组心肌SIRT1,Acfoxo1,Ac-p53及凋亡通路蛋白表达。结果 VCP28预处理可明显改善糖尿病大鼠离体灌流心脏缺血/再灌注后血流动力学指标,降低心肌梗死面积,抑制凋亡信号通路,显著提高SIRT1表达并下调Ac-foxo1及Ac-p53的水平(P<0.01)。结论 VCP28可明显改善糖尿病大鼠离体灌注心脏缺血/再灌注后心功能指标和心肌梗死面积,对糖尿病心肌损伤有明显的保护作用;且SIRT1通路激活可能是VCP28抗糖尿病心肌缺血/再灌注损伤的重要机制。
Objective To investigate the protective effect of adenosine A1 receptor partial agonist VCP28 on myocardial ischemia / reperfusion injury in type 1 diabetic rats and its mechanism. Methods The model of isolated heart ischemia / reperfusion in SD rats with type 1 diabetes mellitus was established. According to sham group, I / R group and I / R + VCP28 (adenosine A1 Receptor partial agonist) group (n = 8). Left ventricular pressure (LVP) was collected and recorded during the course of the experiment. LVDP and ± dp / dt max were measured according to pressure waveforms. The area of myocardial infarction was determined by TTC staining. Western Blot Method to detect myocardial SIRT1, Acfoxo1, Ac-p53 and apoptotic pathway protein expression in each group. Results VCP28 preconditioning could significantly improve hemodynamics after myocardial ischemia / reperfusion in isolated perfused diabetic rats, decrease myocardial infarct size, inhibit apoptosis signaling pathway, significantly increase SIRT1 expression and down-regulate Ac-foxo1 and Ac-p53 (P <0.01). Conclusions VCP28 can significantly improve the cardiac function and myocardial infarction area after myocardial ischemia / reperfusion in isolated diabetic rats, which may have a protective effect on diabetic myocardial injury. The activation of SIRT1 pathway may be the result of VCP28 anti-diabetic myocardial ischemia / reperfusion Important mechanism of perfusion injury.