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目的探讨线粒体ATP敏感性钾通道(mitoKATP)开放剂二氮嗪(DZ)能否减轻氯化锂-匹鲁卡品致痫大鼠海马神经元的氧化应激损伤。方法随机将成年雄性Wistar大鼠84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DZ 5 mg/kg,DZ+5-HD组先用5-HD 8 mg/kg,再用DZ 5 mg/kg,皆腹腔内注射。观察各组大鼠行为学变化,癫痫发作后48 h,用多聚甲醛灌注取脑,石蜡包埋切片,HE和Nissl染色观察大鼠海马神经元的损伤情况。分别在致痫后24 h、48 h断头取脑,分离海马,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。提取海马总DNA,检测海马DNA 8-羟基脱氧鸟苷(8-OHdG)的含量。结果与对照组比较,PILO组大鼠HE和Nissl染色显示海马CA1区和CA3区神经元损伤和丢失明显,海马中MDA的含量升高,SOD、GSH-Px的活力下降,海马DNA 8-OHdG的含量升高(P均<0.05);与PILO组及DZ+5-HD组比较,DZ组大鼠癫痫发作的潜伏期延长,神经元损伤和丢失明显减轻,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,降低海马DNA 8-OHdG的含量(P均<0.05)。DZ的作用能被5-HD阻断。结论 DZ可减轻大鼠癫痫发作后的氧化应激损伤,对癫痫发作具有神经保护作用。
Objective To investigate whether mitochondrial ATP sensitive potassium channel opener diazoxide (DZ) can reduce oxidative stress injury induced by lithium chloride-pilocarpine in hippocampal neurons of epileptic rats. Methods 84 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 were treated with DZ 5 mg / kg and DZ + 5-HD with 5-HD 8 mg / kg before DZ 5 mg / kg, all intraperitoneal injection. The behavioral changes of the rats in each group were observed. Forty-eight hours after the onset of seizure, the brain and paraffin-embedded sections were perfusion with paraformaldehyde. The damage of hippocampal neurons was observed by HE and Nissl staining. The hippocampus were separated from the hippocampus and the contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH- Px) vitality. The total DNA of hippocampus was extracted and the content of DNA 8-OHdG in hippocampus was detected. Results Compared with the control group, HE staining and Nissl staining in PILO group showed that neurons in CA1 and CA3 area of hippocampus were damaged and lost significantly. MDA content in hippocampus and activity of SOD and GSH-Px in hippocampus were decreased. DNA 8-OHdG (P <0.05). Compared with PILO group and DZ + 5-HD group, the latency of epileptic seizures in rats in DZ group was prolonged, the damage and loss of neurons were significantly reduced, the mortality rate in acute phase of seizures decreased, DZ can significantly reduce the content of MDA in hippocampus of rats after seizure, increase the activity of SOD and GSH-Px, and decrease the content of DNA 8-OHdG in hippocampus (all P <0.05). The role of DZ can be blocked by 5-HD. Conclusion DZ can reduce the oxidative stress injury after epileptic seizure in rats and has neuroprotective effects on seizures.