促红细胞生成素后处理在兔蛛网膜下腔出血中的作用

Reversal effect of single intravenous injection of erythropoietin on vasospasm in the basilar artery following subarachnoid hemorrhage

目的 探讨促红细胞生成素（EPO）后处理对家兔蛛网膜下腔出血（SAH）后脑血管痉挛的逆转作用.方法 30只新西兰白兔按照随机数字表法分为5组：Sham组、SAH0组、SAH1组、SAH2组、SAH3组.Sham组假穿刺,其他4组行枕大池穿刺注血的方法造模.Sham组和SAH0组造模24 h后静脉单次注入生理盐水0.1 mL/kg,SAH1组、SAH2组、SAH3组分别静脉单次注入EPO 500 IU/kg、1000 IU/kg、2000 IU/kg.所有动物存造模完成后48 h处死,使用Image Pro Plus 6.0图像分析系统测量分析并比较不同组问基底动脉管腔面积、基底动脉收缩系数以及海马CAI区神经元密度.结果基底动脉形态学观察结果可见Sham组血管管壁无增厚、无增生或坏死：SAH0组、SAH1组血管壁明显增厚,结构紊乱,中膜明显变厚,平滑肌排列紊乱;SAH3组血管内弹力膜皱折,SAH2组血管改变介于SAH1和SAH3组之间.基底动脉管腔面积SAH2组[（0.10±0.01）mm2]、SAH3组[（0.16±0.02）mm2]较SAH0组[（0.07±0.02）mm2]明显增大,基底动脉收缩系数SAH2组（1.22±0.06）、SAH3组（1.15±0.03）较SAH0组（1.31±0.09）明显减小,海马神经元密度SAH3组[（126.8±5.7）个/mml较SAH0组[（99.3±9.6）个/mm]明显增大,差异均有统计学意义（p〈0.05）.结论 在SAH后24h,单次静脉注射EPO不仅可以逆转家兔基底动脉痉挛,还可以减轻其脑神经细胞损伤.

Objective To investigate the reversal effect of intravenous injection of erythropoietin on vasospasm in the basilar artery in rabbits subjected to subarachnoid hemorrhage （SAH）. Methods Thirty male New Zealand adult white rabbits weighing 2.0-2.5 kg were equally randomized into 5 groups： sham-operated group, SAH0 group, SAH1 group, SAH2 group and SAH3 group. SAH models of single-hemorrhage were established by injecting autologous arterial blood （1.0 mL/kg） into the cistema magna in SAH group＇ s rabbits, while animals in the sham-operated group received an injection of normal saline （1.0 mL/kg）. Twenty-four h after SAH, rabbits in the sham-operated group and the SAH0 group were received intravenous injection of normal saline （0.1 mL/kg）, meanwhile, intravenous injection ofr-Hu-EPO at dosages of 500, 1000, or 2000 IU/kg was initiated in the SAHI group, SAH2 group SAH3 group, respectively. All animals were sacrificed by perfusion-fixation 48 h after SAH induction. The cross section areas ofbasilar arteries, corrugation coefficient （CC） of the basilar arteries, and hippocampus normal neuron density of CA1 area were measured by Image-Pro-Plus software. Results Morphology observation on the basilar arteries showed no obvious changes in the sham-operated group, significantly thickened and disorganized vascular walls with thickened tunica media and disorganized smooth muscle in the SAH0 and SAH1 groups; the internal elastic lamina in the SAH3 group was folded. Compared with that in SAH0 group [（0.07±0.02） mm^2], the cross-sectional area of basilar arteries in SAH2 [（0.10±0.01） mm^2] and SAH3 [（0.16±0.02） mm^2] groups were significantly increased （P〈0.05）; the CC in SAH2 （1.22±0.06） and SAH3 （1.15±0.03） groups was significantly lower than that in the SAH0 group （1.31±0.09, P〈0.05）; and the normal neural density ofhippocampus in CA1 area in the SAH3 group [（126.8±5.7） cell/ram] was significantly higher than that in the SAH0 group [（99.3±9.6） cell/mm, P〈0.05]. Conclusion A single intravenous injection of erythropoietin 24 h after SAH can still reverse SAH-induced vasospasm and attenuate injury of neurons.