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目的探讨胰岛素(Ins)通过增加葡萄糖代谢发挥对缺血/再灌注(I/R)心肌的保护作用。方法 54只SD成年大鼠根据灌流底物不同随机分为葡萄糖(Glu)组、丙酮酸(Pyr)组及棕榈酸(PA)组,每组内又随机分为对照(Control)组、I/R组及I/R+Ins组,每组6只。大鼠离体心脏缺血30 min和再灌注1 h制备I/R模型。缺血前30 min持续性灌流Ins(100 U/L)。利用多道生理记录仪检测心脏血流动力学指标:左心室舒张压(LVDP)、左室内压变化速率(±d P/dtmax)及冠脉流量(CF)。采用TTC染色法检测心肌梗死范围。采用Western blot方法检测总Akt(t-Akt)及其磷酸化[p-Akt(Ser473)]水平。结果 I/R+Ins时,Glu组和Pyr组的LVDP、±d P/dtmax和CF显著高于I/R组(P<0.05),梗死面积显著低于I/R组(P<0.01),而PA组的LVDP、±d P/dtmax、CF和梗死面积与I/R组相比并无明显差异。与I/R组相比,I/R+Ins时,Glu组、Pyr组和PA组的p-Akt(Ser473)明显上调(P<0.01,P<0.05),且Glu组p-Akt的上调程度显著高于Pyr组和PA组(P<0.05)。结论 Ins对I/R心肌保护作用依赖于其对葡萄糖代谢的增加,提示增加葡萄糖代谢可以为临床治疗缺血性心脏疾病提供新的治疗方案。
Objective To investigate the protective effect of insulin on myocardial ischemia / reperfusion (I / R) by increasing glucose metabolism. Methods Fifty-four SD adult rats were randomly divided into Glu group, Pyr group and Palmitic acid group according to different perfusion substrates. Each group was randomly divided into Control group, R group and I / R + Ins group, 6 rats in each group. I / R model was prepared after ischemia of rat heart for 30 min and reperfusion for 1 h. Insulin (100 U / L) was continuously perfused 30 minutes before ischemia. Cardiac hemodynamic parameters were measured with LVDP, ± d P / dt max and coronary flow (CF). TTC staining was used to detect the extent of myocardial infarction. The levels of total Akt (t-Akt) and phosphorylated [p-Akt (Ser473)] were detected by Western blot. Results Compared with I / R group, LVDP, ± d P / dtmax and CF in Glu group and Pyr group were significantly higher than those in I / R group (P <0.05) , While LVDP, ± d P / dtmax, CF and infarct size in PA group were not significantly different from those in I / R group. Compared with I / R group, p-Akt (Ser473) in Glu group, Pyr group and PA group was significantly increased (P <0.01, P <0.05) at I / R + The degree was significantly higher than Pyr group and PA group (P <0.05). Conclusion The protective effect of Ins on I / R myocardium depends on its increase of glucose metabolism, suggesting that increasing glucose metabolism may provide a new therapeutic strategy for clinical treatment of ischemic heart disease.