AktGSK-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

摘要:

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。

关键词:

蛋白激酶B/糖原合成酶激酶-3&beta;通路;莱菔硫烷;心脏移植;冷缺血再灌注损伤

Abstract:

 Abstract: 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.

Key words:

 ;Akt/Gsk-3&beta; signaling pathway; sulforaphane; heart transplantation; cold ischemia reperfusion injury