乌司他丁对大鼠蛛网膜下腔出血后迟发性脑血管痉挛的影响及其脑保护作用

目的通过乌司他丁(UTI)对雄性SD大鼠枕大池二次注血建造的蛛网膜下腔出血(SAH)模型的干预,观察其对迟发性脑血管痉挛(delayed cerebral vasospasm,DCVS)的防治及脑保护作用。方法将30只雄性SD大鼠随机分为空白对照组(Normal组)、假注血组(sham组)、注血组(SAH组)和乌司他丁治疗组(SAH+UTI组)。通过枕大池二次注血法建立SAH模型,光镜下观察基底动脉组织学变化和海马CA1区神经元的形态变化,计算血管舒张度(D/T)及海马CA1区神经元密度;应用免疫组化方法检测基底动脉NF-κB的表达。结果神经功能缺损评分:SAH+UTI组评分较SAH组明显改善(P<0.05);基底动脉测量发现,SAH组较Sham组血管周径及D/T值明显减低(P<0.05),SAH+UTI组较SAH组血管周径及D/T值增大(P<0.05);海马CA1区HE染色:与Normal及Sham组比较,SAH组神经元密度明显减少(P<0.05);SAH+UTI组与SAH组比较神经元密度增大(P<0.05);基底动脉NF-κB的表达:SAH组及SAH+UTI组基底动脉NF-κB的表达均较Sham组及Normal组增多(P<0.05);应用乌司他丁可以减轻SAH后NF-κB的表达(P<0.05)。结论乌司他丁可以减轻SAH后DCVS,并减轻神经细胞损伤,改善大鼠SAH后神经功能缺损症状。

Effects of ulinastatin on delayed cerebral vasospasm following subarachnoid hemorrahage in rats and its neuroprotection

Objective To explore the effects of ulinastatin(UTI) on delayed cerebral vasospasm(DCVS) following subarachnoid hemorrahage(SAH) in rats and its neuroprotection.Methods Thirty male Sprague-Dawley rats were randomized into four groups: normal group,sham group,SAH group and SAH+UTI group.SAH model was established by double injection of blood into rat cisterna magna.Brain stem with the basilar artery and hippocampus was taken and sliced.Basilar artery and hippocampus sections were analyzed under light microscope after hematoxylin-eosin staining.The perimeter and D/T value of the basilar artery and density of neurons were measured by image analysis system.The expression of NF-κB in vessel wall of the basilar artery was detected by immunohistochemistry.Results Neurological deficit score: it was remarkably improved in SAH+UTI group compared with that in SAH group(P<0.05).The perimeter and D/T value of the basilar artery were significantly lower in SAH group than in sham group(P<0.05);the perimeter and D/T value in SAH+UTI group were significantly improved compared with those in SAH group(P<0.05).HE staining in CA1 area of hippocampus: Compared with those in sham group and normal group,most neurons in SAH group had necrosis and neuron density was significantly diminished(P<0.05).Compared with those in SAH group,necrosis in SAH+UTI group was much ameliorated and neuron density was significantly increased(P<0.05).NF-κB expression in basilar artery wall: It was apparently decreased in SAH+UTI group compared with that in SAH group,and the gray value was significantly lower(P<0.05). Conclusion Ulinastatin can alleviate the severity of DCVS and alleviate nerve cell damage after SAH,thus improving neurologic deficit symptoms in rats after SAH.