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-  2016 

组蛋白去乙酰化酶抑制剂介导的Akt/Gsk3β通路激活在糖尿病大鼠心肌缺血再灌注损伤中的保护作用 Protection Effect of Histones Deacetylases Inhibitor on Ischemia/Reperfusion Induced Myocardium Injury in Diabetic Rats

Keywords: 组蛋白去乙酰化酶,缺血/再灌注损伤,糖尿病,凋亡

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Abstract:

目的:探讨组蛋白去乙酰化酶(HDAC)抑制剂(TSA)对糖尿病大鼠心肌缺血再灌注(MI/R)损伤是否具有保护作用及其机制。方法:SD大鼠腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型,饲养8周。大鼠麻醉后行机械通气,结扎冠状动脉左前降支(LAD)30 min随后开放120 min以建立心肌缺血再灌注模型。TTC和Evens blue双重染色法测定梗死面积,TUNEL染色检测心肌凋亡程度,免疫印迹法检测蛋白激酶B(Akt)和糖原合酶激酶-3β(Gsk3β)的磷酸化水平以及凋亡相关蛋白Bcl-2,Bax的表达量。结果:HDAC抑制剂能够降低糖尿病大鼠的心肌梗死面积,减轻MI/R损伤所致心肌凋亡;合并给予Akt抑制剂后,TSA的保护作用被抑制;进一步研究表明HDAC抑制剂提高了高糖状态下MI/R损伤后的心肌Akt磷酸化水平,同时也提高了Akt下游蛋白p-Gsk3β的表达量。结论:Akt的激活是HDAC抑制剂发挥糖尿病MI/R损伤保护作用的关键机制,HDAC抑制剂可能是通过Akt/Gsk3β信号通路发挥保护作用

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