摘要
Objective:To investigate the effects of adenovirus(Ad)-mediated hypoxia-inducible factor-1alpha(HIF-1α)gene on proliferation and differentiation of endogenous neural stem cells(NSCs)in rats following intracerebral hemorrhage(ICH)and the underlying mechanisms.Methods:A total of 120 specific pathogen-free,adult,male Sprague-Dawley rats were included in this study.After establishment of ICH models in rats,PBS,Ad,or Ad-HIF-1αwas administered via the ischemic ventricle.On the 1st,7th,14th,21st and 28th d after ICH,rat neurological deficits were scored,doublecortin(DCX)expression in the subventricular zone cells was detected by immunohistochemical staining,and 5-bromo-2’-deoxyuridine(Brdtl)-,BrdU/DCX-,and BrdU/glial fibrillary acidic prolein-posilive cells in the subventricular zone were counted using immumofluorescence method among PBS,Ad,and Ad-HIF-1αgroups.Results:On the 7th,14th,21st and 28th d after ICH,neurological deficit scores in the Ad-HIF-1αgroup were significantly lower than in the PBS and Ad groups(P【0.05).In the Ad-HIF-lαgroup,DCX expression was significantly increased on the 7th d,peaked on the 14th d,and then gradually decreased.In the Ad-HIF-1αgroup,BrdU-positive cells were significantly increased over time course,and significant difference in BrdU-positive cell counts was observed when compared with the PBS and Ad groups at each time point(P【0.01 or 0.05).On the 7th,14th,21st and 28th d after ICH,the number of DCX-,BrdU-,BrdU/DCX-,and BrdU/DCX-positive cells in the Ad-HIF-1αgroup was significantly greater than in the PBS and Ad groups(P【0.05).Conclusions:HIF-1αgene can promote the proliferation,migration and differentiation of endogenous neural stem cells after ICH,thereby contributing to neurofunctional recovery after ICH.
Objective:To investigate the effects of adenovirus(Ad)-mediated hypoxia-inducible factor-1alpha(HIF-1α)gene on proliferation and differentiation of endogenous neural stem cells(NSCs)in rats following intracerebral hemorrhage(ICH)and the underlying mechanisms.Methods:A total of 120 specific pathogen-free,adult,male Sprague-Dawley rats were included in this study.After establishment of ICH models in rats,PBS,Ad,or Ad-HIF-1αwas administered via the ischemic ventricle.On the 1st,7th,14th,21st and 28th d after ICH,rat neurological deficits were scored,doublecortin(DCX)expression in the subventricular zone cells was detected by immunohistochemical staining,and 5-bromo-2'-deoxyuridine(Brdtl)-,BrdU/DCX-,and BrdU/glial fibrillary acidic prolein-posilive cells in the subventricular zone were counted using immumofluorescence method among PBS,Ad,and Ad-HIF-1αgroups.Results:On the 7th,14th,21st and 28th d after ICH,neurological deficit scores in the Ad-HIF-1αgroup were significantly lower than in the PBS and Ad groups(P<0.05).In the Ad-HIF-lαgroup,DCX expression was significantly increased on the 7th d,peaked on the 14th d,and then gradually decreased.In the Ad-HIF-1αgroup,BrdU-positive cells were significantly increased over time course,and significant difference in BrdU-positive cell counts was observed when compared with the PBS and Ad groups at each time point(P<0.01 or 0.05).On the 7th,14th,21st and 28th d after ICH,the number of DCX-,BrdU-,BrdU/DCX-,and BrdU/DCX-positive cells in the Ad-HIF-1αgroup was significantly greater than in the PBS and Ad groups(P<0.05).Conclusions:HIF-1αgene can promote the proliferation,migration and differentiation of endogenous neural stem cells after ICH,thereby contributing to neurofunctional recovery after ICH.
基金
supported by grants from the Natural Science Foundation of Chongqing(No.cstc2012jja10067)
grants from Municipal Educational Commission Foundation of Chongqing(No.kj110309)
