摘要
目的在建立氯化锂-毛果芸香碱癫持续状态模型的基础上,观察内质网应激相关因子CCAAT/增强子结合蛋白同源蛋白(CHOP)和Caspase-12的表达变化,探讨促红细胞生成素(EPO)产生脑保护作用的可能机制。方法 21～30 d SD大鼠96只随机分为对照组(n=32)、氯化锂-毛果芸香碱癫组(n=32)及EPO干预组(n=32),每组按6 h、24 h、48 h、72 h时间点又分为4个亚组,每亚组8只。观察各组大鼠的行为学变化,用免疫组织化学法检测各时间点各组大鼠CHOP及Caspase-12的表达水平。结果氯化锂-毛果芸香碱癫组大鼠海马区CHOP的表达水平明显增加,6 h开始增加,24 h达到高峰,后逐渐下降,至72 h仍高于对照组,与对照组同一时间点比较差异均有统计学意义(Pa<0.05);氯化锂-毛果芸香碱癫组大鼠海马区Caspase-12的表达水平在6 h开始增加,48 h达到高峰,72 h开始下降,但仍高于对照组,与对照组同一时间点比较差异均有统计学意义(Pa<0.05)。EPO干预组海马区CHOP及Caspase-12的表达较同一时间点氯化锂-毛果芸香碱癫组均下降,差异有统计学意义(Pa<0.05)。结论CHOP和Capase-12在癫发作后表达明显增加,提示内质网应激机制在癫性脑损伤的发生发展中具有重要作用;EPO可能通过内质网应激机制产生脑保护作用。
Objective To observe the endoplasmic reticulum stress - related factors CCAAT/enhaneer - binding protei - homologous protein（ CHOP）, Caspase - 12 expression in hippocampus and explore possible mechanism of brain protection by erythropoietin（EPO） in epileptic brain damage of rats induced by lithium - pilocarpine. Methods Ninety - six SD rats aged 21 - 30 d were randomly divided into control group （ n = 32）, lithium - pilocarpine epilepsy group （ n = 32） and EPO treated group （ n = 32 ）, each group were subdivided into 4 groups （n --8 ） at 6 h,24 h,48 h and 72 h. Immunohistochemistry was used to analyze the expressions of CHOP and Caspase - 12 in hippocampus areas of rats, and their behavior changes were observed. Results The expression of CHOP in hippocampus in epilepsy group increased gra- dually,6 h began to increase, reached peak at 24 h, then reduced gradually,but the expression of CHOP in 72 h was still higher than that in control group,there were signifiant difference of CHOP between the both groups at the same time points（ P 〈 0.05）. The expression of Caspase- 12 in hippocampus in epilepsy group increased gradually ,6 h began to increase, and then gradually increased, reached peak at 48 h ,72 h began to decline, but the expressions were still higher than those in control group at the same time points（ Pa 〈 0.05 ）. In the EPO treated group,the level of CHOP and Caspase - 12 in hippocampus at different time points had significant differences compared with those in epilepsy groups（Pa 〈 0. 05）. Conclusions The expressions of CHOP and Caspase - 12 increases dramatically after epileptic discharges, which indicates that the mechanism of the endoplasmic reticulum stress could contribute to the occurrence and development of epileptic brain damage. EPO may produce brain protection by the mechanism of the endoplasmic reticulum stress.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2012年第1期47-49,共3页
Journal of Applied Clinical Pediatrics
