R-型钙通道阻滞剂对自发性蛛网膜下隙出血脑血流量的作用

目的：研究R-型钙通道阻滞剂SNX-482对大鼠自发性蛛网膜下隙出血（SAH）脑血流量减少的改善作用，并与L-型钙通道阻滞剂尼莫地平进行比较。方法：建立大鼠鞍上池SAH模型，分为SAH组、SAH＋尼莫地平组、SAH＋SNX-482组和假手术组。SAH＋尼莫地平组和SAH＋SNX-482组分别于模型建立后第1、2天向脑池内注射尼莫地平5峙或SNX-4825μg，第3天行神经功能评分、荧光微球法测定脑血流量以及脑组织大体病理观察。结果：SAH大鼠模型，据Sugawara大鼠SAH病理分级为中度。3组间神经功能评分差异无统计学意义（P〉0．05）；尼莫地平对脑血流量下降无明显治疗作用（P〉0．05）；SNX-482可减少SAH引起的脑血流量下降（P〈O．05）。结论：R-型钙通道阻滞剂很可能成为有效的SAH脑血管痉挛治疗药物。

Effect of R-type Calcium Channel Antagonist on Cerebral Blood Flow Following Subarachnoid Hemorrhage

Aim： To explore the effect of R-type calcium channel antagonist, SNX-482, on cerebral blood flow following SAH （subarachnoid hemorrhage） and compare it with classic L-type calcium channel antagonist. Methods： Nimodipine 5 μg or SNX-482 5μg was intracisternally instillated respectively one and two days after rats SAH model construction, which was manipulated via autologous arterial blood injection into suprasellar cistern. Neurological status, cerebral blood flow determination with fluorescent microspheres and macroscopic pathological investigation were carried out three days after model construction. Results： This model was defined as moderate SAH according to Sugawara established SAH pathological scale for rats and there was no statistic significance for neurological status among SAH, SAH＋Nimodipine and SAH＋SNX-482 groups （P〉0.05）. Nimodipine had no significant effect on the reduction of cerebral blood flow due to SAH（P〉0.05）, whereas SNX-482 can partially inhibit the reduction of cerebral blood flow（P〈0.05）. Conclusion： R-type calcium channel antagonist has the potential to be a promising drug for vasospasm therapy following SAH.