SIRT1介导VCP28抗1型糖尿病心肌缺血/再灌注损伤的研究

VCP28 protects type 1 diabetic heart against myocardial ischemia/reperfusion injury: role of SIRT 1

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 VCP28 （ adenosine A1 receptor partial agonist） on myocardial is- chemia/reperfusion injury in diabetic rats and to explore its underlying mechanism. Methods Langendorff perfusion of the isolated heart model was established. Type 1 diabetic SD rats were randomly assigned to the following groups （n = 8） ： 1） Sham group, 2） I/ R group and 3） I/R＋VCP28 group （VCP28, adenosine A1 receptor partial agonist; 0.1 nmol/L, 10 min before myocardial ichemia）. Left ventricular pressure and left ventricular developed pressure were measured during the whole period. After the reperfusion, the myo- cardial infarction was evaluated. Additionally, the expressions of SIRT1, Ac-foxol, Ac-p53 and apoptotic related protein were also measured. Results VCP28 treatment markedly improved the cardiac function and reduced myocardial infarction after the reperfusion period. In addition, VCP28 administration also up-regulated the expression of SIRT1 and down-regulated the expressions of Ac-foxol and Ac-p53, thus inhibiting the apoptotic signaling. Conclusion This study showed that VCP28 protected the heart against MI/R in- jury by reducing apoptosis possibly through SIRT1 signaling pathway.