关键词: 海人酸, AKT/ mTOR通路, HIF1α, 大鼠

Abstract: Objective To explore roles of Akt/mTOR signal pathway activation and HIF1α expression in the lesioned hippocampus following 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 anaesthetizeed and a skull hole drilled, ICV injection of KA (1.0 ?g) (KA group), or the same volume of nomal saline (NS group) were 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 indicated 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 changes were observed in both the NS and the sham rats. Conclusion Akt/mTOR signaling pathway was activated and expression of HIF1α was increased in KA-lesioned rats and it maybe modulate the survival of hippocampal neurons.

Key words: Kainic acid, AKT/mTOR, HIF1α, Rat