Akt/mTOR信号通路在海人酸损伤大鼠海马组织中的激活

Activation of Akt/mTOR siganling pathway in rat hippocampus following kainate injection

目的研究Akt/mTOR信号通路在海人酸(KA)诱导的大鼠海马神经元损伤中的激活和HIF1α的表达情况。方法成年SD大鼠随机分为3组,其中2组接受脑室注射,1组为假手术组。大鼠麻醉后颅骨钻孔但侧脑室注射KA1.0μg(KA组)或等体积生理盐水(NS组)或相应位置颅骨钻孔但不予注射(假手术组)。8和16 h及1、3和5 d后,用Western blot观察Akt和mTOR的表达及其磷酸化水平,用免疫组化观察HIF1α的表达情况。结果尼氏染色显示,KA组大鼠海马CA3区1 d时即开始有死亡,5 d时累及CA1区。Akt在KA损伤16 h后就开始激活并持续至第5天;mTOR于第1天开始激活,第3天时达峰值。CA3区的HIF1α于第1天明显升高,CA1区的HIF1α表达则于3 d时明显升高。NS组和假手术组上述各指标变化均不明显。结论 KA诱导激活大鼠海马中Akt/mTOR通路,可能调节神经元的存活。

Objective To explore roles of Akt/mTOR signal pathway activation and HIF1α expression in the lesioned hippocampus following kaimic acid（KA） treatment.Methods Adult Sprague Dawley（SD） rats were radomly divided into three groups,two of them received intracerebroventricular（ICV） injection and one served as the sham group.After rats were anaesthetized and a skull hole drilled,ICV injection of KA（1.0 μg）（KA group）,or the same volume of nomal saline（NS group） was made.Sham group rats underwent skull hole drilling with no injection.8 h,16 h,1 d,3 d and 5 d after KA or NS administration,expression of Akt/phospho-Akt and mTOR/p-mTOR was examined by Western blot,and HIF1α expression was evaluated by immunohistochemistry.Results Nissl staining revealed an initial neuronal death in the hippocampus CA3 region 1 d after KA injection and in the CA1 region at 5 d.Western blot showed that Akt was activated at 16 h and persisted for at least 5 d,an initial activation of mTOR started at 1 d,peaked at 3 d and then returned to baseline level.Expression of HIF1 was increased significantly at 1 d in the hippocampus CA3 region and at 3 d in the CA1 region.No significant change was found in both the NS and the sham rats.Conclusion Akt/mTOR signaling pathway was activated and expres-sion of HIF1α increased in KA-lesioned rats and may modulate the survival of hippocampal neurons.