磷酸二酯酶5抑制剂促进大鼠脑缺血再灌注后神经及血管再生的研究

目的探讨磷酸二酯酶5抑制剂西地那非对大鼠脑缺血再灌注后海马神经前体细胞标记物微管相关蛋白增殖及血管内皮细胞生长因子(VEGF)表达的影响。方法雄性SD大鼠75只,随机分为假手术组5只,局灶性脑缺血再灌注组(单纯缺血组)35只及局灶性脑缺血+西地那非组(西地那非组)35只。西地那非组在大脑中动脉局灶缺血模型再灌注后2 h喂服西地那非3 d。单纯缺血组和西地那非组在术后2 h、1 d、3 d、5 d、7 d、10 d和14 d检测神经功能缺损评分。免疫组织化学方法检测各时间点海马神经前体细胞标记物微管相关蛋白阳性细胞及梗死灶周围VEGF的吸光度值。结果假手术组几乎无微管相关蛋白表达。与单纯缺血组比较,西地那非组7 d、10 d、14 d神经功能缺损评分明显升高,差异有统计学意义(P<0.05);西地那非组5 d、7 d、10 d、14 d微管相关蛋白明显高于单纯缺血组,差异有统计学意义(P<0.05,P<0.01);西地那非组3 d、5 d、7 d、10 d VEGF明显高于单纯缺血组,差异有统计学意义(P<0.05,P<0.01)。结论西地那非能够促进大鼠脑缺血再灌注后急性期神经及血管再生,改善神经功能。

Phosphodiesterase 5 inhibitor sildenafil stimulates neurogenesis and revascularization in rats following cerebral ischemia reperfusion

Objective To study the effect of sildenafil,a phosphodiesterase 5 inhibitor,on proliferation of neural precursor cell marker doublecortin(DCX) in hippocampus and expression of vascular endothelial growth factor(VEGF) in rats following ischemia reperfusion(I/R).Methods Seventy -five male SD rats were randomly divided into sham operation group(n= 5),I/R group(n= 35) and I/R+sildenafil group(n=35).Two hours after a middle cerebral artery ischemia model was established,rats in I/R+sildenafil group were given sildenafil for 3 days.Nerve function was scored for I/R group and I/R+sildenafil group at 2 h and on days 1,3,5,7,10 and 14 after operation. DCX positive cells in hippocampus and VEGF expression were detected at different time points by immunohistochemistry.Results Almost no DCX was expressed in sham operation group.The nerve function deficit score was significantly higher in I/R+sildenafil group than in I/R group on days 7,10 and 14 after operation(P<0.05),The DCX positive cells and VEGF expression level were significantly higher in I/R+sildenafil group than in I/R group on days 5,7, 10,14 and on days 3,5,7,10,respectively after operation(P<0.05,P<0.01).Conclusion Sildenafil can promote neurogenesis and revascularization,and improve nerve function in rats following cerebral I/R.