ABSTRACT
Objective:To investigate the relationship between the serum high mobility group box 1 (HMGB1) level and children with febrile convulsion(FC) and epileptic seizures in the future.Methods:A total of 359 children with first-episode FC occurring in January 2014 to January 2017 admitted to the Department of Pediatrics, Henan Provincial People′s Hospital, were enrolled in the FC group.One hundred children without FC were enrolled in the fever control group, and 100 healthy children were enrolled in the healthy control group.Children with FC were followed for 18 months and their seizures were recorded.Serum HMGB1 and inflammatory response indexes were measured in all subjects, and the diagnostic value of HMGB1 for FC was analyzed.Other data were used to analyze the correlation between HMGB1 and the conversion of FC into epilepsy.Results:The level of serum HMGB1 in the FC group were hig-her than those in the healthy control group and the fever control group, and the differences were statistically significant [(3.04±1.01) μg/L, (5.09±1.45) μg/L vs.(8.32±2.27) μg/L, all P<0.01]. serum HMGB1 level in children with FC was positively correlated with interleukin(IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and white blood cell (WBC) ( r=0.364, 0.173, 0.227, 0.235, 0.247, all P<0.05). There were significant differences in HMGB1 levels between groups with different duration and types of convulsions [(8.11±2.15) μg/L vs.(10.19±2.51) μg/L, (7.63±1.93) μg/L vs.(9.83±2.25) μg/L, all P<0.05]; HMGB1 level diagnosis of FC was better [area under the receiver′s operating characteristic curve (AUC)=0.843 (95% CI: 0.811-0.873)]; Serum HMGB1 in children with epilepsy with FC was higher than that without conversion to epilepsy, and the difference was statistically significant [(8.18±2.14) μg/L vs.(8.95±2.73) μg/L, P<0.05]; However, its performance in predicting the conversion of FC to epilepsy was not high [AUC=0.596 (95% CI: 0.544-0.691)]; Multivariate regression analysis showed that it was not an independent influencing factor of FC to epilepsy [odd ratio( OR)=1.929, P=0.222]. Conclusions:Serum HMGB1 levels in children with FC are related to the onset, severity and type of fever, and are one of the influencing factors affecting the conversion of FC to epilepsy, but not the independent factors.
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.