胰岛素保护缺血/再灌注心肌依赖于葡萄糖代谢

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(P0.05),梗死面积显著低于I/R组(P0.01),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(P0.01,P0.05),且Glu组p-Akt的上调程度显著高于Pyr组和PA组(P0.05)。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。

Insulin protects heart against ischemia/reperfusion injury through stimulation of glucose metabolism

AIM To investigate whether insulin (Ins) protects heart against ischemia/reperfusion (I/R) injury through stimulation of glucose metabolism. METHODS Fifty-four rats were randomly divided into three groups: glucose group (Glu), pyruvate group (Pyr) and palmitate group (PA), each group was randomly divided into Control group, I/R group, I/R+Ins group, six rats in each group. Hearts were subjected to 30 min of myocardial ischemia and 1 h of reperfusion and insulin was intravenously infused at 100 U/L for 1 h, 30 min before ischemia in vitro. Hemodynamic parameters (LVDP, ±dP/dtmax and CF) were detected by multi-channel physiology recorder, phosphorylation and total levels of Akt were determined by Western blot and cardiac infarct size was evaluated by staining with TTC. RESULTS Compared with those in control, LVDP, ±dP/dtmax and CF decreased in Glu, Pyr and PA groups following I/R (P<0. 01). After insulin treatment, LVDP, ±dP/dtmax and CF increased in Glu and Pyr groups (P<0. 05), but LVDP, ±dP/dtmax and CF did not change in PA group compared with those in I/R. Infarct size did not change in Glu, Pyr and PA groups compared with that in I/R, infarct size decreased in Glu and Pyr groups (P<0. 01), whereas infarct size in PA group did not decrease after insulin treatment. Western blot showed no obvious difference in t-Akt and p-Akt (Ser473) levels between Glu, Pyr and PA groups. Compared with those in I/R, up-regulated p-Akt (Ser473) was found in Glu, Pyr and PA groups (P<0.05). Glu group showed a further up-regulated p-Akt (Ser473) (P<0.05), whereas p-Akt (Ser473) level was not significantly different between Pyr group and PA group after insulin treatment. CONCLUSION Insulin protects heart against acute myocardial I/R injury through stimulation of glucose metabolism, which validates the concept that stimulating of glucose metabolism is a novel therapy for ischemic heart disease.Low HDL-C is associated with the risk CHD in Chinese Han population.