AKT信号通路通过亚低温对大鼠局脑缺血再灌注损伤神经元的保护作用

目的通过检测AKT及Bcl-2蛋白的表达,探讨亚低温对局脑缺血再灌注后神经元存活的影响。方法用线拴法制作大鼠大脑中动脉闭塞（MCAO）局脑缺血再灌注模型,将36只SD大鼠随机分成假手术组、常温缺血再灌注组和亚低温缺血再灌注组,缺血组分别缺血6h再灌注4h、24h、72h、1w（n=4）后处死,亚低温组于缺血后13~14min实施病灶侧亚低温持续4h。免疫组织化学法检测AKT、Bcl-2蛋白的表达,电镜检测自噬小体。结果不同缺血时间再灌注4h,亚低温组比常温组缺血侧半暗带AKT表达水平显著增高（P〈0.05）,Bcl-2表达明显降低（P〈0.01）;亚低温组自噬小体明显减少。结论病灶侧亚低温通过促进缺血半暗带脑组织AKT表达,抑制Bcl-2表达,从而抑制神经元凋亡,抑制自噬的产生,从而对神经元起保护作用,促进脑缺血后神经功能恢复。

AKT signaling pathway through the local of mild hypothermia on cerebral ischemia-reperfusion in rats neuronal injury protection

Objective To explore the therapeutic effectiveness of local mild hypothermia on expression of AKT and Bcl-2 to study the relation of apoptosis inhibit protein AKT in rats after local cerebral ischemia and reperfusion injury. Methods The local cerebral ischemia and reperfusion model of rats were achieved by intraluminal middle cerebral artery occlusion （MCAO）.The adult rats（36） were randomly divided into sham-operation group,normothermia ischemia and reperfusion group and hypothermia ischemia and reperfusion group .The ischemic groups were respectively further divided into subject ischemia for 6h respectively and then all reperfused for 4h、24h、72h、1w（n=4）, and before killing per time point. Local mild hypothermia was achieved 13~14 minutes after ischemia and maintained 4 hours. The expression of AKT, Bcl-2 were assayed by immunohistochemistry. Results Compared with the normothermia groups, local mild hypothermia greatly increased the expression of AKT and obviously decreased the expression of Bcl-2 in penumbra at the differently ischemia time and reperfused for 4h（P0.05 or P0.01）.Mild hypothermia group marked decline in autophagic vesicles. Conclusion The local mild hypothermia can accelerate the recovery of the neurological outcome.The neuroprotection of mild hypothermia may be related to the inhibition of the activation of Bcl-2,enhancing AKT expression in penumbra.