抑制GSK-3β减轻大鼠急性心肌缺血/再灌注损伤的作用

Glycogen synthase kinase-3β inhibition protects heart from acute ischemia / reperfusion injury

目的:评估糖原合酶激酶-3β(GSK-3β)抑制剂TDZD-8减轻大鼠急性心肌缺血/再灌注损伤(MIRI)的作用,并探讨此作用是否与其下调NF-κB、抑制炎症有关。方法:取健康雄性SD大鼠60只,随机分为缺血/再灌注(I/R)组、I/R+TDZD组、I/R+载体(Vehicle,V)组及假手术(Sham)组。大鼠局部心肌缺血30 min,再灌注3 h。用TTC染色计算心肌梗死面积,HE染色及ELISA法评估心肌组织中中性粒细胞浸润及炎性因子(TNF-α和IL-6)的变化;用Western blot测定心肌组织中NF-κB、GSK-3β磷酸化的水平。结果:TDZD-8能明显降低心肌梗死的面积和心肌组织中性粒细胞浸润、抑制NF-κB激活以及心肌源性TNF-α和IL-6的浓度(P<0.01)。结论:GSK-3β抑制剂TDZD-8能够减轻MIRI,其作用可能与其抑制NF-κB的激活及炎症反应有关。

AIM：To investigate the effects of TDZD-8, a GSK-3β inhibitor, on acute myocardial ischemia/reperfusion injury and to determine whether the protection is associated with the downregulation of NF-κB and the inhibition of inflammation. METHODS： Sixty healthy male Sprague Dawley rats were randomly divided into ischemia/reperfusion （I/R group）, ischemia/reperfusion＋drug group （I/R＋D group）, ischemia/reperfusion＋vehicle group （I/R＋V group） and sham group. Rats were subjected to 30 min ischemia followed by 3 h reperfusion. Myocardial infarct sizes were detected by TTC staining and myocardial tissue neutrophil infiltration. Changes in inflammatory factors were evaluated using HE staining and ELISA method. Phosphorylation of NF-κB and GSK-3β was measured by Western blotting. RESULTS： TDZD-8 reduced the infarct size and neutrophil infiltration （P〈0.01） and inhibited NF-κB activation （P〈0.01） and levels of cardiac-derived TNF-α and IL-6 （P〈0.01）. CONCLUSION： GSK-3β inhibitor, TDZD-8, can protect myocardial ischemia/reperfusion injury and may be related to the inhibition of NF-κB activation and the inhibition of inflammation.