一氧化氮缓释剂对兔蛛网膜下腔出血迟发性脑血管痉挛保护作用的研究

Prevention and Reversal of Experimental Posthemorrhagic Vasospasm by Intrathecally Injection of Nitric Oxide from a Controlled-release Polymer

目的合成一氧化氮(NO)缓释剂并观察该缓释剂对兔蛛网膜下腔出血(SAH)模型迟发性脑血管痉挛(CVS)的影响。方法将二乙烯三胺/一氧化氮聚合物与聚[1,3-双(对羧基苯氧基)丙烷-癸二酸](PcPP-SA)用喷雾干燥法合成缓释剂;枕大池二次注血法建立兔蛛网膜下腔出血模型,并随机分为实验组,空载体组及对照组,实验组鞘内注射缓释剂,空载体组鞘内注射PcPP-SA,对照组鞘内注射等量生理盐水。分别于4、7、10d处死动物。测定脑脊液中NO浓度及基底动脉标本内径周长。结果实验组NO浓度各时间段均显著高于另外两组(P<0.05),空载体组与对照组之间无明显差别。实验组基底动脉内径周长各时间段均显著长于另外两组(P<0.05),空载体组与对照组之间无明显差别。结论一氧化氮缓释剂对兔SAH模型CVS有治疗作用。

Objective To synthesize the contorlled-release polymer of nitric oxide, and observe its effects on delayed cerebral vasospasm following experimental subarachnoid hemorrhage in rabbits. Method compose retarder with DETA/NO and PcPP-SA, （ CPP： SA = 20：80） with spray drying method. Randomly group 36 New-Zealand white rabbits into the experimental group, vacant carriage group and controlled group. Make the model of Subarachnoid Hemorrhage in Rabbits by double injection of blood at cisterna magna. Intrath- ecally Inject retarder in the experimental group, the PcPP-SA in the vacant carriage group, and normal saline in the controlled group. Execute rabbits respectively after 4, 7 and 10 days, and collect cerebrospinal Fluid and specimen of arteriae basilaris. Measure density of NO in cerebrospinal Fluid, dye HE in arteriae basilaris, and analyze perimeter of interior diameter of arteriae basilaris. Results Over various intervals, the densities of NO of the experimental group are obviously higher than the other two groups（P 〈 0. 05 ）, and there is no remarkable difference between the vacant carriage group and the controlled group. Over various intervals, the perimeters of interior diameter of arteriae basilaris of the experimental group are remarkably longer than those of the other two groups, and there is no noticeable difference between the vacant carriage group and the controlled group of SAH. Conclusion The controlled-release polymer of NO has therapeutical effect on CVS following rabbit SAH.