【摘要】 【目的】探讨较大剂量血管紧张素-(1-7)预处理对大鼠心肌缺血再灌注损伤的影响及其信号机制。【方法】48只SD大鼠随机分为4组,每组12只:缺血再灌注对照组、血管紧张素-(1-7)预处理组、血管紧张素-(1-7)预处理加磷脂酰肌醇-3激酶(PI3K)抑制剂Wortmannin处理组、Wortmannin处理对照组,观察较大剂量血管紧张素-(1-7)预处理对大鼠离体缺血再灌注心脏左心室收缩压、冠状动脉流量、肌酸磷酸激酶和乳酸脱氢酶释放、心肌梗死范围以及心肌蛋白激酶B(Akt)、糖原合成酶激酶-3β(GSK-3β)磷酸化的影响。【结果】与缺血再灌注对照组相比,血管紧张素-(1-7)预处理组心脏左心室收缩压、冠状动脉流量显著提高,冠状动脉循环流出液中肌酸磷酸激酶、乳酸脱氢酶含量降低,心肌梗死范围减小,心肌磷酸化Akt(Ser473)、磷酸化GSK-3β(Ser9)水平增高,PI3K抑制剂Wortmannin能够抑制血管紧张素-(1-7)预处理所致的Akt、GSK-3β磷酸化,但只能部分消除血管紧张素-(1-7)预处理的心脏保护效应。【结论】较大剂量血管紧张素-(1-7)预处理能够减轻大鼠离体心脏缺血再灌注损伤,PI3K/Akt/GSK-3β信号通路参与介导血管紧张素-(1-7)预处理的心脏保护作用。更多还原

【Abstract】 [Objective] To explore the effects of large dose angiotensin-(1-7) preconditioning on isolated rat heart ischemia reperfusion injury and investigate the signal mechanism underlying the role of angiotensin-(1-7) preconditioning. [Methods] Forty eight rats were randomly separated into 4 groups: ischemia reperfusion (IR) control group, IR treated with angiotensin-(1-7) preconditioning group, IR treated with angiotensin-(1-7) preconditioning and phosphatidylinositol-3-kinase (PI3K) inhibitor wortmannin group, and IR treated with wortmannin alone to evaluate the effects of large dose angiotensin-(1-7) preconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase (CK) and lactate dehydrogenase (LDH) release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt (Ser473), phospho-glycogen synthase kinase-3β (Ser9). [Results] Left ventricular systole pressure and coronary artery flow were improved significantly, and the release of CK and LDH was reduced significantly with obvious reduction of myocardial infarction size in angiotensin-(1-7) preconditioning group as compared to ischemia reperfusion control group. Meanwhile, the levels of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3β (Ser9) were increased in angiotensin-(1-7) preconditioning group compared with these in ischemia reperfusion control group. Wortmannin inhibited the increase of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3β (Ser9) induced by angiotensin-(1-7) preconditioning, but only abolished partly the cardioprotection of angiotensin-(1-7) preconditioning. [Conclusion] Large dose angiotensin-(1-7) preconditioning attenuates isolated rat heart ischemia reperfusion injury. The phosphorylation of protein kinase B/ glycogen synthase kinase-3β signal pathway is involved in the cardioprotection of angiotensin-(1-7) preconditioning.更多还原