褪黑素对癫痫大鼠海马氧化应激及神经元凋亡的影响

摘要

Objective To investigate the effects of melatonin on oxidative stress and neuronal apoptosis in hippocampus of epileptic rats and the mechanism. Methods Seventy-two adult male Sprague-Dawley rats were equally divided into control group, model group, low dose group and high dose group. The model group was injected coriamyrtin 50μg/kg in the lateral ventricle, while the low dose group and high dose group were injected melatonin 20 mg/kg and 60 mg/kg, respectively, 30 minutes before injection of coriamyrtin. The contents of malo-ndialdehyde (MDA) and superoxide dismutase (SOD) were detected with ultraviolet spectrophotometer, the apoptosis was detected with TU-NEL, and the ultrastructural changes of neurons and mitochondria in hippocampal CA3 region were observed with electron microscopy, af-ter 60 minutes of epilepsy. Results The neurons and mitochondria in hippocampus were damaged, the number of apoptotic cells significant-ly increased (P<0.001), the content of SOD decreased (P<0.001), and the content of MDA increased (P<0.001) in the model group, com-pared with the control group. In the low dose group, the ultrastructural damage relieved, the number of apoptotic cells decreased (P<0.01), the content of SOD increased (P<0.05), and the content of MDA decreased (P<0.05);and for the high dose group, the ultrastructural damage relieved very much, the number of apoptotic cells decreased (P<0.001) and was not significantly different from the control group (P>0.05), SOD increased (P<0.001), and MDA decreased (P<0.001), compared with the model group. Conclusion Exogenous melatonin may signifi-cantly reduce neuronal apoptosis in rat hippocampal after epilepsy, and high dose is more effective, which may relate with resistance of oxi-dative stress, alleviate neuronal mitochondrial damage.%目的：探讨褪黑素对癫痫大鼠海马氧化应激及神经元凋亡的影响及其机制。方法成年雄性Sprague-Dawley大鼠72只等分为对照组、模型组、褪黑素低剂量组和褪黑素高剂量组。模型组侧脑室注射马桑内酯50μg/kg，褪黑素低、高剂量组分别于腹腔注射褪黑素20 mg/kg和60 mg/kg后30 min，侧脑室注射马桑内酯50μg/kg。癫痫持续60 min后，采用紫外分光光度计检测丙二醛(MDA)、超氧化物歧化酶(SOD)的含量；原位末端标记法(TUNEL法)检测大鼠海马CA3区神经元凋亡；电镜观察海马CA3区神经元及其线粒体改变。结果与对照组相比，模型组海马神经元、线粒体出现明显超微结构损伤，凋亡细胞数显著增多(P<0.001)，海马SOD显著降低(P<0.001)，MDA显著升高(P<0.001)。与模型组相比，褪黑素低剂量组大鼠海马神经元、线粒体超微结构损伤有所改善，凋亡细胞数明显减少(P<0.01)，SOD升高(P<0.05)，MDA降低(P<0.05)；褪黑素高剂量组大鼠海马神经元、线粒体超微结构损伤明显改善，凋亡细胞数显著减少(P<0.001)，且与对照组相比无显著性差异(P>0.05)， SOD显著升高(P<0.001)， MDA显著降低(P<0.001)。结论给予外源性褪黑素可明显减少癫痫大鼠海马神经元凋亡，高剂量效果更佳，其作用机制可能涉及褪黑素对抗氧化应激反应，减轻神经元、线粒体损伤。