The protective effect of JNK inhibitor SP600125 on hippocampal neurons in rats with status epilepsy / 中华行为医学与脑科学杂志

ABSTRACT

Objective To explore the protective effect and probable mechanism of JNK inhibitor SP600125 on hippocampal neurons in rats with status epilepsy following lithium?pilocarpine. Methods 48 Wistar rats,in accordance with the random number table,were divided into control,status epilepticus ( SE) and JNK in?hibitor SP600125 group ( SP ) . HE staining and fluorescent TUNEL method were used to observe pathological changes and neuronal apoptosis in the hippocampal area of rats in each group. Western blot was applied to detect the phosphorylation expression of JNK and its downstream effector molecule c?JUN in hippocampal tissues of rats in each group. Results Compared with control group,neuronal loss and apoptosis in CA3 area of hippocampus in SE group were significant (percentage of TUNEL positive cells (26.34±3.04)%, P<0.05). The mortality of rats was significantly decreased and neuronal loss and apoptosis were obviously reduced in SP group than in SE group ( mor?tality in SP and SE group6.25%,37.5% respectively, P<0.05). Meanwhile,the expression levels of phospho?JNK and phospho?c?JUN were significantly increased in hippocampus of rats in SE group ( The relative OD values respectively 0.447±0.025,0.552±0.035, P<0.05 compared with Control group). After treated with SP600125 in SP group,the phosphorylation levels of JNK and c?JUN were obviously decreased ( The relative OD values respec?tively 0.211±0.016,0.237±0.028, P<0.05 compared with SE group). Conclusion JNK inhibitor SP600125 may play an important protective effect on neurons in the rat hippocampus after status epilepticus through inhibition of JNK and c?JUN phosphorylation.