文章摘要
糖原合成酶激酶3β在糖尿病减弱七氟醚后处理心肌保护中的作用
Effect of glycogen synthesis kinanse 3β in the diabetic attenuates the myocardial protection of sevoflurane
  
DOI：10.12089/jca.2018.10.016
中文关键词: 麻醉药,吸入  心肌再灌注损伤  腺相关病毒
英文关键词: Anesthetic, inhalation  Myocardial reperfusion injury  Adeno-associated virus
基金项目:山西省科技厅自然基金委员会科研课题(201601D101121)
作者单位E-mail
张一强 030001,太原市,山西大医院麻醉科  
贺建东 030001,太原市,山西大医院麻醉科  
韩冲芳 030001,太原市,山西大医院麻醉科 hanchongfang2003@foxmail.com 
方爱莉 030001,太原市,山西大医院麻醉科  
王晓鹏 030001,太原市,山西大医院麻醉科  
杨文曲 030001,太原市,山西大医院麻醉科  
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中文摘要:
      
目的 通过糖原合成酶激酶3β(GSK-3β)的过表达,探讨其在糖尿病减弱七氟醚后处理心肌保护中的作用。
方法 2月龄健康清洁级雄性SD大鼠60只,体重200～300 g,采用随机对照法分为五组: 假手术组(Sham组)、正常大鼠IR组(NI组)、正常大鼠IR+七氟醚后处理组(NS组)、糖尿病大鼠缺血-再灌注(IR)+七氟醚后处理组(DS组)、正常大鼠GSK-3β过表达+IR+七氟醚后处理组(GS组),每组12只。采用腹腔单次注射链脲佐菌素(STZ)60 mg/kg的
方法 制备糖尿病大鼠模型。采用左开胸心脏左前降支冠状动脉结扎30 min后再灌注120 min的
方法 制备IR模型。采用在IR模型构建前2周经尾静脉注射包装有GSK-3β突变型基因的腺相关病毒(AAV9型)
方法 处理构建GSK-3β过表达。观察大鼠IR模型制备过程中是否有心肌缺血的ECG表现(ST段抬高,出现宽大Q波及心律失常等),120 min后经腹主动脉取血,检测肌钙蛋白I(cTnI)浓度;处死大鼠取心脏,计算心肌梗死体积;光镜下观察心肌病理学损伤;采用Western blot法测定心肌GSK-3β和caspase-3含量。
结果 与Sham组比较,NI组、NS组、DS组、GS组cTnI浓度明显升高,梗死体积明显增大,病理损伤加重,GSK-3β和caspase-3含量明显升高(P<0.05);与NI组比较,NS组cTnI浓度明显降低,梗死体积明显减小,病理损伤减轻,GSK-3β和caspase-3含量明显降低(P<0.05);与NS组比较,DS组、GS组cTnI浓度明显升高,梗死体积明显增大,病理损伤加重,GSK-3β和caspase-3含量明显升高(P<0.05);DS组和GS组cTnI浓度、心肌梗死体积、GSK-3β和caspase-3含量差异无统计学意义。
结论 GSK-3β过表达可加重大鼠心肌IR损伤,七氟醚后处理对糖尿病大鼠心肌IR时的保护作用减弱可能是通过GSK途径导致的。
英文摘要:
      
Objective To evaluate the effect of glycogen synthesis kinanse 3β (GSK-3β) in the diabetic attenuates the myocardial protection of sevoflurane in rats.
Methods Two monthes old healthy clean male SD rats, weighing 210 - 300 g, were given single intraperitoneal injection of streptozotocin (STZ) 60 mg/kg to establish diabetic rat model, 12 rats were allocated into group DS (diabetic rats with ischemia-reperfusion and sevoflurane post-procession). Another 48 healthy SD rats simultaneously fed were divided into four groups (n = 12) according to the principle of random control: group Sham (sham operation), group NI (ischemia-reperfusion), group NS (ischemia-reperfusion and sevoflurane post-procession), and group GS (ischemia-reperfusion and GSK-3β overexpression). Ischemia-reperfusion model was induced by occlusion of the left coronary artery for 30 min followed by 120 min reperfusion. The post-procession of sevoflurane was followed by inhalation of 2.5％ sevoflurane for 5 min from 1 min before reperfusion. GSK-3β overexpression was performed by tail-vein injection of GSK overexpressing recombinant adenovirus (AAV9) one week before the ischemia-reperfusion model was constructed. The ECG performance of myocardial ischemia was observed in the preparation of ischemia-reperfusion model in each group (stern elevation, large Q wave and arrhythmia). Abdominal aortic blood was extracted and the concentration of cTnI was tested after 120 min. And then the rats were executed to remove the heart. Myocardial infarct size and myocardial pathological damage were measured. The expression of GSK-3β and caspase-3 were detected by Western blot.
Results Compared with Sham group, groups NI, NS, DS and GS ECG showed ST segment elevation, wide Q wave, increased number of arrhythmia per minute, increased cardiac troponin concentration, increased infarct size, increased pathological damage, and up-regulated expression of caspase-3 (P < 0.05). Compared with group NI, the cardiac troponin concentration decreased in group NS, infarct size and pathological damage, caspase-3 expression were down-regulated (P < 0.05). Compared with group NS, groups DS and GS showed ST segment elevation and wide Q waves, increased arrhythmia per minute, increased troponin concentration, increased infarct size, increased pathological damage and up-regulated expression of caspase-3 (P < 0.05). Compared with group DS, the difference between the above indicators was not statistically significant in group GS.
Conclusion Overexpression of GSK-3β recombinant adenovirus can increase myocardial IR injury in diabetic rats and reduce the protective effect of sevoflurane on myocardial IR in diabetic rats. The protective mechanism of sevoflurane on diabetic myocardium is through signal transduction path of GSK.
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