关键词: 雷帕霉素, 癫痫, PI3K, AKt, 小胶质细胞

Abstract:

Objective To investigate the protective effect of mTOR inhibitor Rapamycin（RAPA）on post⁃epileptic brain injury and the regulation mechanism of PI3K/AKt signaling pathway. Methods 40 male Sprague⁃Dawley（SD）rats were randomly divided into 4 groups：control group，KA group，KA+RAPA 5 mg/kg group andKA+RAPA 10 mg/kg group. A model of epilepsy in rats was made by intraperitoneal injection of kanic acid（KA）.The control group was injected with normal saline only. RAPA was administered intraperitoneally 2 h beforeKA⁃induced epilepsy. Rats were sacrificed 24 h after epilepsy and the cerebral cortex was removed. Western blotand qRT⁃ PCR was used to detect PI3K，AKt and mTOR protein and mRNA expression，Immunohistochemicalstaining was used to observe microglia activation；Western blot was used to detect the protein expression of NF⁃kBand IL⁃6 in the inflammation pathway. Results The protein and mRNA levels of PI3K、AKt and mTOR，theprotein levels of NF⁃kB and IL⁃6，microglia activation significantly increased after KA⁃induced epilepsy，but theseeffects were inhibited by RAPA treatment. Further analysis found the effect of RAPA dose 10 mg/kg is more obvious.Conclusions The mTOR inhibitor RAPA can decrease the PI3K/AKt signaling pathway，microglia activation andreduce inflammatory response after epilepsy，thus protecting brain damage after epilepsy.

Key words: RAPA, epilepsy, PI3K, AKt, microglia