异丙嗪对大鼠急性前脑缺血再灌注线粒体通透性转换影响.docVIP

异丙嗪对大鼠急性前脑缺血再灌注线粒体通透性转换影响 　【摘要】 目的：观察不同浓度异丙嗪对大鼠急性前脑缺血再灌注线粒体通透性转换(MPT)的影响，并从分子水平探讨其神经保护作用的机制。方法：用夹闭双侧颈总动脉再开放法制作全脑缺血模型。大鼠随机分为缺血再灌注+异丙嗪组(治疗组)，假手术+异丙嗪组(假手术组)，缺血再灌注+NS(模型组)；术前1h静注不同浓度异丙嗪(5，15，45mg/kg)，术后6h　3组均分离前脑线粒体，用分光光度法检测MPT值。结果：模型组分别与治疗组(异丙嗪浓度为5mg/kg时)和假手术组(异丙嗪浓度为5，15mg/kg时)比较，模型组MPT值减小更为明显(Plt;001)；组内比较，异丙嗪浓度为5，15mg/kg时比浓度为45mg/kg时抑制MPT值减小的作用更为显著(Plt;005)。结论：异丙嗪能抑制缺血再灌注所致的MPT值的改变，因而可以通过阻止神经细胞线粒体的损伤发挥脑保护作用。 【关键词】 异丙嗪 缺血再灌注 脑 线粒体膜的通透性转换 神经细胞保护 ［Abstract］Objective: To observe the effects of promethazine at different concentrations on mitochondrial permeability transition(MPT)of acute ischemia_reperfusion in rat fore_brain, and to explore the neuron_protective mechanism in mole_cular level. Methods: Acute ischemia_reperfusion models in rat brain were made by reopening both sides common carotid artery after clipping. Rats were assigned into ischemia_reperfusion with promethazine group,sham operation with prome_thazine group and ischemia_reperfusion withnormal saline group. Promethazine at different concentrations(5，15，45mg/kg)were injected one hour before operation, the mitochondria were extracted from rat fore_head 6 hours after operation. The MPT value in all the groups was determined by spectrophotometer. Results: Compared with the groups of ischemia_reperfusion with promethazine(5mg/kg)and sham operation with promethazine(5，15mg/kg), the MPT value decreased significantly in the ischemia_reperfusion with normal saline group(Plt;001). In the same group, the effect of promethazine(5，15mg/kg)was more obvious, compared with 45mg/kg(Plt;005). Conclusion: Promethazine at various concentrations can inhibit the changes of MPT value induced by ischemia_reperfusion in rat fore_brain，therefore the neuron_protective effect may be produced by preventing neuron mitochondrial impairment. ［Key Words］promethazine; ischemia_reperfusion, brain; mitochondrial permeability transition; protection of neuron 研究表明，具有突出抗组胺作用的吩噻嗪类化合物异丙嗪对动物急性脑缺血再灌注损伤有保护作用，且推断与对抗脂质过氧化并减轻脑水肿有关［1］。最近发现，一系列