糖原合成酶激酶3β在心肌缺血／再灌注损伤及保护中的作用  

The roles glycogen synthase kinase 3β in myocardial ischemia/reperfusion injury and its protection

作　　者：程怡[1] 薛富善[2] 李瑞萍[2] 刘高谱 

机构地区：[1]首都医科大学北京安贞医院麻醉科,100029 [2]中国医学科学院北京协和医学院整形外科医院麻醉科

出　　处：《国际麻醉学与复苏杂志》2015年第9期847-852,共6页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金（81170128）

摘　　要：背景糖原合成酶激酶3β（glycogen synthase kinase 3β，GSK-3β）是一种多功能丝氨酸廓氨酸激酶，在细胞代谢、生长、分化以及凋亡中发挥重要作用。GSK-3β通过磷酸化作用参与细胞内多条信号转导通路的调节。目的综述GSK-3β在心肌缺血／再灌注损伤（ischemia／reperfusion injury，I/RI）及相关保护措施中的作用。内容活化的GSK-3β通过放大炎症反应、诱导线粒体通透性转换孔不可逆性高水平开放以及激活多条凋亡途径参与心肌I／RI的发生，而抑制GSK-3β活性能明显提高心肌对I／RI的耐受性。另外，GSK-3β及其信号转导通路在病态心肌的异常改变是阻断多种干预措施发挥保护作用的重要原因。趋向恢复GSK-3β相关信号转导通路的正常反应性将有助于解决心肌I／RI相关研究的临床转化困局。Background Glycogen synthase kinase 3β （GSK-3β） is a multifunctional serine threonine kinase that plays important roles in cell metabolism, growth, differentiation and apoptosis. GSK-3β is a vital component of several signal transduction pathways with the ability to phosphorylate the substrates. Objective This review will focus on issues regarding the roles of GSK-3β in myocardial ischemia/reperfusion injury （I/RI） and its protection. Content The actived GSK-3β can amplify the inflammatory response, induce the irreversibly high level opening of the mitochondrial permeability transition pore and activate the apoptofic pathways in turns that aggravates myocardial I/RI, whereas depressing activation of GSK-3β can significantly improve the tolerance of heart to the I/RI. In addition, the abnormal status of GSK-3β and the related signal transduction pathways are the critical reasons for the impaired cardioprotection of many protective interventions in the comorbidities. Trend The recovery of sensibility of GSK-3β and the related signal transduction pathways may help to address the difficulty of translating the outcomes of the basic researches on myocardial I/RI to the clinic.

关 键 词：糖原合成酶激酶3Β 心肌缺血/再灌注损伤 炎症反应 线粒体通透性转换孔 细胞凋亡 

分 类 号：R614[医药卫生—麻醉学]