海人酸致癫痫间持续状态大鼠海马神经元线粒体损伤及caspase-3表达

Mitochondrial ultrastructural damage and caspase-3 expression in the hippocampal neurons during kainic acid induced status epilepticus in rats

目的观察海人酸诱导的癫痫间持续状态(status ep ilepticus,SE)大鼠海马CA3区神经元线粒体损伤及caspase-3的表达。方法用海人酸诱导大鼠SE 2 h;于SE终止后第3、6、24 h取海马,光镜观察神经元的变化,并用电镜进一步观察线粒体的超微结构;免疫组化方法检测caspase-3的表达。结果SE终止后3h电镜下可见到线粒体嵴的肿胀和膜的崩解;SE后24 h神经元呈坏死样改变;caspase-3的表达在SE后6 h开始增加(与对照组比较,P<0.05),于第24 h明显增高(P<0.01)。结论在实验性SE模型中早期即出现线粒体超微结构的损伤,其后出现caspase-3的表达增高及神经元形态的改变,提示线粒体的损伤是SE后神经元损伤的关键环节。

Objective To observe the mitochondrial damage and caspase-3 expression in the hippocampal CA3neurons during status epilepticus（SE） induced with kainic acid. Methods SE was induced in adult male Wistar rats with kainic acid. In 3.6, and 24 hours after SE, the rats were killed and the brain sections were made. We observed the neuronal damage histologically by light microscope and mitochondrial ultrastructure with electron microscope, The immunohistochemical staining was used to examine caspase-3 expression. Results By electron microscope examination, in 3 hours after SE, mitochondrial were showed swelling cristae and ruptured membrane, and the neurons were necrotic at the 24h time point. Caspase-3 expression increased at 6 hours after SE（P〈0. 05）, and increased much more at the 24h time point（P〈0. 01）. Conclusions Our results show that mitochondria were damaged in the early period of SE. The increment of caspase-3 expression and the alteration of neuronal morphology can be seen a few hours later. This suggests that mitochondrial damage is critical in the process of neuronal injury after SE.