山莨菪碱不同方式给药对亚低温治疗大鼠脑缺血的影响

Effects of anisodamine administered by different routes on cerebral ischemia treated with mild hypothermia

目的：探讨不同途径用山莨菪碱对亚低温治疗大鼠脑缺血再灌注损伤的影响。方法：利用前脑缺血动物模型，观察缺血再灌注后海马神经元的病理改变及一氧化氮（ＮＯ）、一氧化氮合成酶（ＮＯＳ）的变化。结果：大鼠海马中央区（ＣＡ１区）存活神经元计数：亚低温大剂量山莨菪碱颈动脉灌注组＞亚低温组，亚低温大剂量山莨菪碱静脉用药组＞常温组。ＮＯＳ活性则表现为亚低温大剂量山莨菪碱颈动脉灌注组＜亚低温组，亚低温大剂量山莨菪碱静脉用药组和亚低温小剂量山莨菪碱颈动脉灌注组＜常温组。而且亚低温及亚低温复合用山莨菪碱均能显著抑制ＮＯ值的升高，减轻大量ＮＯ生成所导致的细胞毒性作用。结论：亚低温，大剂量山莨菪碱颈动脉灌注可以提高亚低温治疗效果（优于静脉滴注法），能够减轻海马迟发性神经元损伤；并抑制ＮＯＳ活性，减少ＮＯ的生成。

Objective:To investigate effects of mild hypothermia (MH) combined with different dosage of anisodamine administered by different routes on cerebral ischemia and reperfusion injury.Methods:The change in neuronal histologic examination,nitric oxide synthase (NOS) and nitric oxide(NO) in hippocampus were assayed in rats after cerebral ischemia and reperfusion.Results:Survived neuronal counts in hippocampal CA1 region in MH combined with high dose of anisodamine via jugular artery (MHTA) were higher than in MH group,and they were also high in MH combined with high dose of anisodamine via femoral vein (MHTV) compared with normothermic group (NT).Similarly,NOS activities were markedly decreased in MHTA group than that in MH group,and they were also low in MH combined with low dose of anisodamine via jugular artery and MHTV group compared with NT group.In addition,both MH and MH combined with anisodamine treatment could significantly inhibit the elevation of NO levels.Conclusions:Mild hypothermia could reduce delayed neuron injury in hippocampus,and a large dose of anisodamine administered through the jugular artery could improve its therapeutic effect,and it appears to be superior to treatment via femoral vein.The benefical effect of MHTA may be associated with inhibition of NOS activity and reduction of NO release.