Akt/GSK-3β通路介导调控莱菔硫烷减轻心脏移植缺血再灌注损伤的研究  

Sulforaphane preconditioning attenuates myocardial cold ischemia reperfusion injury of heart transplantation of rats through Akt/GSK-3β signaling pathway

作　　者：伊雪 杨学慧 杨述亮 石莺 邬鹏宇 王耕银 陈乃耀 高木火[3] 高毅哲[3] 李占清[3] 

机构地区：[1]厦门医学院病理与病理生理学教研室,福建厦门361008 [2]华北理工大学附属医院胸心外科,河北唐山063000 [3]福建省厦门市第二医院(厦门医学院附属医院)胸心外科,福建厦门361021

出　　处：《中国现代医学杂志》2017年第9期8-12,共5页China Journal of Modern Medicine

基　　金：福建省自然科学基金(No:2016D014);福建省医学创新课题(No:2015-CXB-47);福建省厦门市科技惠民项目(No:3502Z20164057)

摘　　要：目的探讨蛋白激酶B(Akt)/糖原合成酶激酶-3β(GSK-3β)信号通路对莱菔硫烷(SFN)预处理减轻大鼠心肌冷缺血再灌注损伤(IRI)的作用机制。方法 64例健康雄性SD大鼠随机分为4组:IRI组、SFN组、阻滞剂LY294002+IRI(LY+IRI)组、阻滞剂LY294002+SFN预处理(LY+SFN)组,将冷藏于心肌保护液(组氨酸-色氨酸-酮戊二酸盐液)9 h的供体心脏移植到受体大鼠的腹腔,复制同种大鼠异体异位心脏移植模型,术后24 h取供体心脏心肌组织,采用免疫组织化学法(IHC)和Western blot检测Akt、磷酸化Akt(p-Akt)、GSK-3β、磷酸化GSK-3β(p-GSK-3β)蛋白的表达。结果 IHC法和Western bolt检测各种蛋白结果显示,与IRI组比较,SFN组p-Akt和p-GSK-3β蛋白表达升高(P<0.05)。应用阻滞剂LY294002后,SFN+LY组与LY+IRI组的p-Akt和p-GSK-3β蛋白表达比较,差异无统计学意义(P>0.05)。结论 SFN能通过Akt/GSK-3β信号通路减轻心脏移植心肌冷缺血再灌注损伤。Objective To explore the role of Akt/Gsk-3β signaling pathway in sulforaphane （SFN） protecting rats from cold myocardial ischemia-reperfusion injury during heart transplantation. Methods Sixty-four health male Sprague-Dawley （SD） rats were randomly divided into 4 groups, i.e. ischemia reperfusion injury group （IRI group）, sulforaphane group （SFN group）, LY294002＋ ischemia reperfusion injury （LY＋IRI group）, and LY294002＋ sulforaphane group （LY＋SFN group）. Isogeneic heterotopic heart transplantation model was established according to Li＇s method. Donor hearts storaged in histidine-tryptophan-ketoglutarate solution for 9 h were transplanted into the abdominal cavities of recipient rats to establish rat models of heterotopic heart transplantation. Akt, p-Akt, GSK-3β and p-GSK-3β protein expressions in the grafts were detected by immunohistochemistry and Western bolt 24 h after reperfusion. Results Compared with the IRI group, p-Akt and p-GSK-3β levels increased in the SFN group （P 〈 0.05）. After using blocker LY294002, there was no significant difference in the expression of p-Akt or p-GSK-3β between the LY＋SFN group and the LY＋IRI group （P 〉 0.05）. Conclusions SFN reduces cold ischemia reperfusion injury in heart transplantation of rats through activating Akt/ GSK-3β signaling pathway.

关 键 词：蛋白激酶B/糖原合成酶激酶-3β通路 莱菔硫烷 心脏移植 冷缺血再灌注损伤 

分 类 号：R654.2[医药卫生—外科学]