Q.L.Chen.et.al,Diabetesmellitusabrogatesthecardioprotectionof

sufentanilagainstischaemia/reperfusioninjurybyalteringglycogen

synthasekinase-3b,ActaAnaesthesiolScand

Abstract

Background:Sufentaniliswidelyusedinclinicalanaesthesiabecauseofitsprotectiveeffectsagainstischaemia/reperfusioninjury.Diabetesmellituselevatestheactivityofglycogensynthasekinase-3b(GSK-3b),therebyincreasingthepermeabilityofmitochondrialtransitionpore.ThisstudyinvestigatedtheroleofGSK-3binamelioratingthecardioprotectiveeffectofsufentanilpost-conditioningindiabeticrats.

Methods:Streptozotocin-induceddiabeticratsandagematchednon-diabeticratsweresubjectedto30minofischaemiaandminofreperfusion.Fiveminutesbeforereperfusion,ratswereadministeredoneofthefollowing:avehicle,sufentanil(1mg/kg),oraGSK-3binhibitorSB(0.6mg/kg).Myocardialinfarctsize,cardiactroponinI,andtheactivityofGSK-3bwerethenassessed.

Results:Sufentanilpost-conditioningsignificantlyreducedmyocardialinfarctsizeinthenon-diabetic,butnotindiabeticrats.SBreducedinfarctsizeinbothdiabeticandnondiabeticanimals.Sufentanil-inducedphospho-GSK-3bwasreduced5minafterreperfusionindiabeticrats,butnotinnondiabeticrats.

Conclusions:Sufentaniltreatmentwasineffectiveinpreventingagainstischaemia/reperfusionindiabeticrats,whichisassociatedwiththeactivationofGSK-3b.OurresultsalsosuggestthatdirectinhibitionofGSK-3bmayprovideastrategytoprotectdiabeticheartsagainstischaemia/reperfusioninjury.

摘要：

背景：舒芬太尼因为其对抗缺血再灌注损伤起到保护作用，在临床麻醉中得到广泛使用。糖尿病增加了糖原合酶-3β（GSK-3β）的活性，从而增加了线粒体转换孔的渗透性。本实验探讨了GSK-3β在减弱糖尿病大鼠舒芬太尼后处理的心肌保护作用中的影响。

方法：链脲霉素诱导的糖尿病大鼠和年龄相仿的非糖尿病大鼠均接受30分钟缺血和分钟的再灌注。再灌注前5分钟，给大鼠分别注射：舒芬太尼（1μg/kg）或GSK-3β阻滞剂SB（0.6mg/kg）。检测心肌梗死面积、心肌肌钙蛋白I和GSK-3β活性。

结果：非糖尿病组舒芬太尼后处理显著减少了心肌梗死的面积，而在糖尿病组未发现该现象。SB均减少了糖尿病组和非糖尿病组大鼠心肌梗死面积。注射舒芬太尼的糖尿病组大鼠再灌注5分钟后磷酸化GSK-3β有所减少，该现象未发生在非糖尿病组。

结论：舒芬太尼治疗对糖尿病大鼠缺血再灌注的没有保护作用，这和GSK-3β的活性有关。我们的实验结果证实了直接阻断GSK-3β可以对糖尿病心脏提供一个有效保护作用，以对抗缺血再灌注损伤。