美满霉素对癫痫大鼠海马神经元凋亡的影响

EFFECT OF MINOCYCLINE ON APOPTOSIS OF HIPPOCAMPAL NEURONS IN EPILEPTICRATS

目的探讨美满霉素(minocycline,MC)对癫痫模型大鼠海马神经元的抗凋亡保护作用。方法将大鼠随机分为3组:生理盐水对照组(NS组),海人酸致痫组(KA组)和美满霉素预处理+海人酸组(MC+KA组)。以免疫组化法检测各组大鼠造模后2h、8h和24h海马部位Cytochrome C(CytC)免疫反应性。采用半定量RT-PCR和免疫组化法检测24h、48h caspase-3 mRNA和caspase-3表达情况。结果在KA致痫后2hCytC即开始有表达,8h达到高峰,24h表达减少,而MC预处理明显减弱此效应。caspase-3 mRNA的含量及caspase-3免疫反应性在24h时间点三组之间无明显差异,在48h时间点,KA组明显高于对照组(P<0.05),MC预处理则明显拮抗KA诱导的caspase-3高表达。结论 KA致痫能诱导大鼠海马神经元凋亡,而MC能通过抑制凋亡途径对海马神经元发挥神经保护作用。

Objective To investigate the protective effect of minocycline on apoptosis of hippocampal neurons in epileptic rats.Methods The rats were randomly divided into 3 groups： normal saline control （NS）, kainic acid （KA） and minocycline pretreatment plus kainic acid （MC ＋ KA）.The level of Cytochrome C （Cyt C） in rat hippocampus was detected by immunohistochemical staining 2h, 8h and 24h after modeling.Caspase -3 mRNA and protein were detected by semi-quantitative RT-PCR and immunohistochemistry respectively 24h, 48h after modeling.Results Cytochrome C began to express at 2h after the KA-induced epilepsy peaked at 8h,and decreased at 24h, while the minocycline pretreatment significantly attenuated this effect. Caspase-3 mRNA levels and caspase-3 immunoreactivity were not significantly different among 3 groups at 24h, while KA was significantly higher than NS at 48h （P0.05）, and minocycline pretreatment obviously antagonized KA-induced caspase-3 expression（P0.05）.Conclusion KA-induced seizures can induce hippocampal neuronal apoptosis of rats, while minocycline can play a neural protective effect of hippocampal neurons by inhibiting the apoptosis pathway.