促红细胞生成素对大鼠蛛网膜下腔出血后血管痉挛的防治作用

目的 探讨促红细胞生成素（EPO）对大鼠蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）的影响及其机制。方法 将60只成年SD大鼠随机分为正常组（6只）、假手术组（18只）、SAH组（18只）、EPO组（18只）；假手术组、SAH组合EPO组根据取材时间有分为1、3、7 d三亚组，每亚组6只。采用枕大池二次注血法建立SAH模型。EPO组建模成功后30 min内腹腔注射EPO（3 000 IU/kg，1次/d）。建模成功后1、3、7 d采用取材基底动脉行HE染色测量基底动脉管径及管壁厚度，采用免疫组化检测基底动脉血管壁核转录因子-κB（NF-κB）及内皮细胞型一氧化碳合酶（eNOS）的表达。结果 SAH后1、3、7 d，假手术组基底动脉管径、管壁厚度、NF-κB和eNOS表达水平与正常组无统计学差异（P>0.05）；与假手术组相比，SAH组各时间点基底动脉管径均明显减小（P<0.05），管壁厚度均明显增加（P<0.05），NF-κB表达水平均明显增加（P<0.05），eNOS表达水平均明显降低（P<0.05）；与SAH组相比，EPO组基底动脉管径、管壁厚度均明显改善（P<0.05），NF-κB表达水平均明显降低（P<0.05），eNOS表达水平均明显增加。结论 EPO能够显著改善大鼠SAH后CVS，机制可能是通过上调eNOS的表达、抑制NF-κB的表达来实现的。

Preventive and therapeutic effects of erythropoietin on cerebral vasospasm after subarachnoid hemorrhage in rats

Objective To observe the effect of erythropoietin (EPO) on the cerebral vasospasm after subarachnoid hemorrhage (SAH) and its mechanism in rats. Methods Sixty SD rats were randomly divided into normal (n=6), SAH (n=18), sham operation (n=18) and treatment groups (n=18). Each rat received intraperitoneal injection of EPO (3000IU/kg) within 30 minutes after SAH in the treatment group and1 day. Each rat in sham and SAH groups received the intraperitoneal injection of isovolumic physiologic saline once a day. Six rats were sacrificed respectively 1, 3 and 7 days after establishment of SAH model in SAH, sham and EPO treatment groups. The rats in sham group were sacrificed at 1 day, 3 days and 7 days after successful modeling in order to take basilar arteries. The basilar artery spasm was observed after hematoxylin-eosin staining. The expressions of nuclear factor-kappa B (NF-κB) and endothelial nitric oxide synthase (eNOS) in the walls of the basilar arteries were detected by immunohistochemical technique in all the groups 1, 3 and 7 days after SAH. Results The diameters of the basilar arteries were significantly bigger in normal and sham operation groups than that in the EPO treatment group (P<0.05), which was significantly bigger than that in the SAH group 1, 3 and 7 days after SAH (P<0.05). The basilar arteries walls were significantly thicker in SAH group than that in the EPO treatment group (P<0.05), which was significantly thicker than those in the normal and sham operation groups 1, 3 and 7 days after SAH (P<0.05). The levels of eNOS expressions were significantly higher in the normal and sham operation groups than that in EPO treatment group (P<0.05), which was significantly higher than that in the SAH group 1, 3 and 7 days after SAH (P<0.05). The level of NF-κB expressions were significantly lower in the normal and sham operation groups than that in EPO treatment group (P<0.05), which was significantly lower than that in SAH group 1, 3 and 7 days after SAH (P<0.05). Conclusions That EPO relives cerebral vasospasm after SAH may be achieved by upregulating the expression of eNOS and inhibiting the expression of NF-κB in the vessel walls in the rats.