CHOP在癫痫内质网应激脑损伤中的作用及其信号机制研究

Recent studies have shown that endoplasmic reticulum stress involves in epileptic brain damage. CHOP is a key pro-apoptotic molecule in endoplasmic reticulum stress. Our preliminary study demonstrated that CHOP was high expression in the epileptic brain tissue, speculating CHOP involved in the pathogenesis of epilepsy. However, its specific role and mechanism is far from clear. Therefore, firstly，this project intends to establish status epilepticus and chronic temporal lobe epilepsy rat model on the basis of preliminary study. Using molecular biology methods, to detect the experession distribution and levels of CHOP under different duration of rat epilepsy. And to analyse the correlation of CHOP with hippocampal neuronal damage.Sceondly, konck-down CHOP with siRNA technology，to observe the changes of seizure in rat and the extent of hippocapal neuronal injury. At the same time, to detect the expression trends of different downstream apoptotic molecules mediated by CHOP. Through research mentioned above, to explore the role of CHOP on endoplasmic reticulum stress mediated epileptic brain injury and its possible mechanism. This study may provide theoretical foundation and experimental data for the research and development of new drugs in epileptic brain protection.

近来研究表明，内质网应激参与了癫痫脑损伤。CHOP是内质网应激促凋亡的关键分子，我们前期研究发现其在癫痫脑组织中表达增加，推测CHOP可能参与了癫痫的病理损伤过程，但其具体作用及机制还远未阐明。为此，本研究拟在前期研究基础上，首先建立癫痫持续状态及慢性颞叶癫痫大鼠模型，应用分子生物学方法检测CHOP在大鼠癫痫不同时程下表达分布与水平，分析与海马神经元损伤的相关性；其次，运用siRNA干扰技术敲减CHOP后，观察对大鼠癫痫发作潜伏期、频率、程度、脑电变化及海马神经元的损伤变化，同时检测CHOP介导的下游不同凋亡分子的走向，探讨CHOP在癫痫脑损伤中的作用及可能机制。为癫痫脑保护新药研发提供理论基础和实验数据。