基于血管新生与神经发生探讨依达拉奉对缺血性脑卒中大鼠的作用与机制

Edaravone protects a rat model of stroke through promoting angiogenesis and neurogenesis

目的探讨依达拉奉对缺血性脑卒中大鼠血管新生和神经发生的影响。方法将SD大鼠分为对照组、缺血性脑卒中组、依达拉奉低剂量、高剂量组;后3组构建大脑中动脉闭塞/再灌注模型,然后各组持续尾静脉注射生理盐水和依达拉奉,持续21 d,结束后进行神经功能评分,取脑组织并进行2,3,5-氯化三苯四唑(2,3,5-triphenyltetrazolium chloride, TTC)染色、免疫荧光染色和Western blot检测。结果 (1)依达拉奉显著降低缺血性脑卒中大鼠神经功能评分(P<0.05);(2)依达拉奉显著增加半影区血小板-内皮细胞粘附分子(Platelet endothelial cell adhesion molecule-1,PECAM-1/CD31)与齿状回区域5-溴脱氧尿嘧啶核苷(5-Bromo-2-deoxyUridine, BrdU)表达(P<0.05);(3)依达拉奉显著提高半影区血管内皮生长因子(Vascular endothelial growth factor, VEGF)与海马组织中脑源性神经生长因子(Brain-derived neurotrophic factor, BDNF)表达水平(P<0.05)。结论依达拉奉可能通过介导血管新生与神经发生来改善缺血性脑卒中造成的神经功能缺损。

Objective To investigate the effect of edaravone on angiogenesis and neurogenesis in rats with ischemic stroke.Methods SD rats were divided into Control group, ischemic stroke group, low-dose and high-dose edaravone groups. The middle cerebral artery ischemia/reperfusion(MCAO/R) model was established in each group, and then saline and edaravone i.v. were continuously administrated for 21 days. The neurological score was assessed, and the brains were taken for TTC staining, immunofluorescence staining and Western blot detection.Results(1) Edaravone significantly reduced the neurological scores of rats with ischemic stroke(P<0.05).(2) Edaravone significantly increased the expression of CD31 in the penumbra and BrdU in the dentate gyrus(P<0.05).(3) Edaravone significantly increased the expression of VEGF in penumbra and BDNF in the hippocampus(P<0.05).Conclusion Edaravone can improve the neurological dysfunction caused by ischemic stroke by mediating angiogenesis and neurogenesis.