AdipoR1/STAT3通路在异丙酚后处理保护糖尿病大鼠心肌缺血再灌注损伤中的作用

Role of AdipoR1/STAT3 pathway in propofol postprocessing in protecting myocardial ischemia reperfusion injury in diabetic rats

目的:探讨异丙酚后处理保护糖尿病大鼠心肌缺血再灌注损伤中AdipoR1/STAT3通路的作用。方法:在Ⅰ型糖尿病大鼠模型及心脏特异性APN受体1(AdipoR1)基因敲除和信号转导及转录激活因子3(STAT3)基因敲除小鼠模型上进行在体缺血再灌注及异丙酚(丙泊酚)后处理(PPC)实验,结合脂联素(APN)腺病毒转染确认APN在糖尿病心脏恢复对PPC敏感性中的作用。结合AdipoR1和/或STAT3 siRNA的转染,在原代分离培养的大鼠及基因敲除小鼠心肌细胞及H9C2细胞中进行缺氧再复氧及PPC实验。结果:脂联素(APN)合用异丙酚(丙泊酚)后处理(PPC)治疗增加了糖尿病心肌磷酸化STAT3及AdipoR1的含量,而第一型血红素氧化酶(HO-1)或AdipoR2的蛋白表达,没有显著改变,差异无统计学意义(P>0.05);联合治疗后,AdipoR1蛋白表达显著高于单独使用APN时,差异有统计学意义(P<0.05)。结论:PPC在糖尿病心肌中可能不是通过激活HO-1/STAT3通路减轻缺血再灌注造成的心肌细胞凋亡及自噬,而APN可通过激活AdipoR1/STAT3通路恢复糖尿病心脏对PPC的敏感性。

Objective To investigate the protective effect of propofol postprocessing on AdipoR1/STAT3 pathway in diabetic rats with myocardial ischemia reperfusion injury.Methods In vivo experiments were conducted in type I diabetes rats and in the heart specific APN receptor 1(AdipoR1)knockout and signal transducer and activator of transcription 3(STAT3)knockout mice models in vivo after ischemia reperfusion and propofol postprocessing(PPC).Adenovirus transfection with adiponectin(APN)confirmed the role of APN in diabetic heart recovery and PPC sensitivity.Combined with the transfection of AdipoR1 and/or STAT3 siRNA,hypoxia reoxygenation and PPC experiments were carried out in primary isolated and cultured rat and gene knockout mouse cardiomyocytes and H9C2 cells.Results The treatment of APN combined with propofol postprocessing(PPC)increased the phosphorylation of STAT3 and AdipoR1 in diabetic myocardium,but the protein expression of type I heme oxygenase(HO-1)or AdipoR2 did not change significantly(P>0.05).After combined treatment,the expression of AdipoR1 protein was significantly higher than that of APN alone(P<0.05).Conclusion PPC may not alleviate cardiomyocyte apoptosis and autophagy by activating HO-1/STAT3 pathway in diabetic myocardium,but APN can restore the sensitivity of diabetic heart to PPC through activating AdipoR1/STAT3 pathway.