Effect of Sirolimus attenuating kainic acid 3 induced epilepsy in mice / 中华实用儿科临床杂志

ABSTRACT

Objective To explore the therapeutic mechanism of in response to kainic acid－induced epilepsy in mice. Methods Sixty mice Were randomly divided into control group,model group and loW－dose Sirolimus group, medium－dose and high－dose Sirolimus groups. Prevention and therapeutic administration Were used in the Sirolimus loW,medium and high dose groups. One Week before model establishment,intraperitoneal injection of Sirolimus 1 mg／kg,3 mg／kg and 9 mg／kg Were given once a day,but the model group and the control group Were injected intra﹣peritoneally the same dose of 9 g／L saline. One Week after the preventive administration,all mice except the control group,Were intraperitoneally injected 30 mg／kg kainate solution,and the control group Was injected an equal dose of 9 g／L saline. Mice Were treated 1 Week after the establishment of the models. The number of mice With epileptic symp﹣toms and the number of epileptic seizures,the seizure time and the average number of episodes Were recorded,the Mor﹣ris Water maze test Was performed on the mice,and the arrival time,sWimming distance and number of crossing times of the mice Were collected. The expression levels of mTOR pathWay－related protein gene and the number of apoptotic cells in hippocampus Were detected in hippocampus of mice. Results Epilepsy symptoms appeared earlier in the model group after modeling,and the epileptoid－like symptoms Were significantly delayed in each group(P﹦0. 001 9). The epilepsy grading model group Was significantly higher than that of other groups. The mouse seizure time on the 6th day after modeling Was significantly higher than that on the 3rd day after modeling. The time required for the model epileptic mouse to reach the platform and the sWimming length Was significantly more than that of the control group( P ﹦0. 000 1),While the number of the mice traversing the platform Was significantly loWer(P﹦0. 000 2),and the admi﹣nistration group Was significantly relieved. The gene expression levels of mTOR pathWay key proteins mTOR and S6 in the hippocampus of mice in the model group Were significantly up－regulated(P﹦0. 000 1). Simultaneously,different doses of Sirolimus could significantly doWn － regulate PI3K,AKT,mTOR,and S6 gene expression levels( P ﹦0. 000 1). Compared With the control group,the gray ratios of p－PI3K,p－AKT,p－mTOR and p－S6 and normal PI3K,AKT,mTOR and S6 protein in the model group Were significantly higher(P﹦0. 000 1),and Sirolimus Was also observed. It Was significantly doWn－regulated after administration(P﹦0. 000 1). Conclusions Sirolimus can signifi﹣cantly inhibit the over－activation of mTOR signaling pathWay in the hippocampal region of kainic acid－induced epi﹣lepsy mice,thereby alleviating the symptoms of epilepsy in mice and increasing learning and memory.