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目的观察线粒体ATP敏感性钾通道(mitoKATP)开放剂二氮嗪(DZ)对氯化锂-匹鲁卡品致痫大鼠海马神经元超微结构及自由基的影响,探讨mitoKATP开放剂对癫痫发作后神经元的保护机制。方法随机将成年雄性Wistar大鼠80只,分为对照组、癫痫组(PILO组)、DZ组(DZ组)、DZ+5-羟基癸酸(5-HD)组(DZ+5-HD组),后两组用氯化锂-匹鲁卡品制作癫痫持续状态模型之前,DZ组用DZ5mg/kg,DZ+5-HD组先用5-HD8mg/kg,再用DZ5mg/kg,皆腹腔内注射。观察各组大鼠行为学变化,分别在致痫后4、24、48h断头取脑,分离海马,电镜观察海马神经元的超微结构,检测海马中丙二醛(MDA)的含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活力。结果与对照组比较,PILO组与DZ+5-HD组可见神经元数目明显减少,细胞肿胀,细胞器减少,胞核内染色质凝聚,线粒体肿胀,嵴缺失,重者线粒体明显空泡化,以癫痫发作后48h最显著;DZ组大鼠癫痫发作的潜伏期延长,神经元损伤明显减轻,癫痫发作急性期的死亡率降低,DZ能明显降低大鼠癫痫发作后海马中MDA的含量,提高SOD、GSH-Px的活力,其作用能被5-HD阻断。结论 DZ可能通过降低大鼠癫痫发作后自由基的水平,提高抗氧化系统的反应性,减轻氧化应激损伤,从而减轻神经元的损伤,起到神经保护作用。
Objective To observe the effects of mitochondria ATP-sensitive potassium channel (DZ) on ultrastructure and free radicals of hippocampal neurons in epileptic rats induced by lithium chloride-pilocarpine and to investigate the effect of mitoKATP opener on epilepsy Protection mechanism of neurons after the attack. Methods Eighty adult male Wistar rats were randomly divided into control group, epilepsy group (PILO group), DZ group (DZ group), DZ + 5-HD group ), The last two groups before using lithium chloride - pilocarpine status epilepticus model, DZ group with DZ5mg / kg, DZ + 5-HD group with 5-HD8mg / kg, then DZ5mg / kg, all abdominal cavity Internal injection. The behavioral changes of the rats in each group were observed. The brain was decapitated at 4, 24 and 48 h after epileptic seizure, the ultrastructure of hippocampal neurons was observed by electron microscopy and the content of malondialdehyde (MDA) Oxidative dismutase (SOD), glutathione peroxidase (GSH-Px) activity. Results Compared with the control group, the numbers of neurons in PILO group and DZ + 5-HD group were significantly decreased, cell swelling, organelles decreased, chromatin condensation in nucleus, mitochondria swelling and crest disappearance, DZ group had longer latency of epileptic seizures, neuronal damage was significantly reduced, the mortality of acute seizures decreased, DZ can significantly reduce the content of MDA in the hippocampus after seizures, increase the activity of SOD, The viability of GSH-Px, its role can be blocked by 5-HD. Conclusion DZ may play a neuroprotective role by decreasing the level of free radicals after epileptic seizures, increasing the reactivity of antioxidant system, reducing the oxidative stress injury, reducing the damage of neurons.