盐酸法舒地尔对蛛网膜下腔出血后血管痉挛的实验研究

Effect of fasudil hydrochloride on cerebral vasospasm following experimental subarachnoid hemorrhage

目的通过建立大鼠蛛网膜下腔出血(SAH)模型,探讨盐酸法舒地尔对蛛网膜下腔出血后血管痉挛的缓解作用和神经保护作用,并与尼莫地平对比,观察疗效。方法通过枕大池二次注血法建立大鼠SAH模型,观察基底动脉和海马神经元形态变化,测量基底动脉管径和管壁厚度,计算海马CA1区神经元密度,检测基底动脉内皮型一氧化氮合成酶(eNOS)的表达。结果各组模型大鼠的基底动脉均出现血管痉挛,海马CA1区正常神经元数目明显减少,多数神经元发生变性,基底动脉的eNOS表达明显减弱。但注射法舒地尔组与其他模型组相比能较大程度的缓解以上变化,具有统计学差异(P<0.05),且优于尼莫地平。结论法舒地尔可以有效缓解SAH后的迟发性脑血管痉挛,具有神经保护作用,其缓解迟发性脑血管痉挛作用和神经保护作用与动脉壁产生的一氧化氮(NO)有关。

Objective To explore the mitigative effect on vasospasm and neural protective effect of fasudil hydrochloride on rat models of subarachnoid hemorrhage （SAH）,with nimodipine as a control for the therapeutic effect.Methods SAH model was induced by double blood injection into cisterna magna of rats. The morphological changes of basilar artery and neurons of hippocampus were observed. The diameter and wall thickness of basilar artery were measured and the neuron density in the CA1 hippocampal field was calculated. The expression of endothelial nitric oxide synthase （eNOS） in basilar artery was detected.Results In all model groups,the vasospasm of basilar artery occurred,the amount of normal neurons in the CA1 hippocampal field was remarkedly decreased,degenerative changes occurred in the majority of neurons,and the expression of eNOS in basilar artery was decreased. But in fasudil hydrochloride treated group,all the changes were significantly mitigated. There was statistical significance compared with the other two groups （P0.05）. The effect of fasudil hydrochloride was better than that of nimodipine.Conclusion Fasudil hydrochloride can attenuate the delayed cerebral vasospasm and protect the neurons after SAH,which is associated with the production of nitric oxide in the vessel wall of cerebral arteries.