[Therapeutic effect of hypoxia-inducible factor-1alpha on focal cerebral ischemia: experiment with rats].
OBJECTIVE
To construct a recombinant adenoviral vector carrying HIF-1alpha gene and explore the therapeutic effect of HIF-1alpha on focal cerebral ischemia in adult rats.


METHODS
The AdEasy System was used to construct the recombinant adenoviral vector carrying HIF-1alpha gene and green fluorescent protein and PCR was used to identify the HIF-1alpha gene. Middle cerebral artery occlusion (MCAo) and reperfusion models were established and divided into Ad-HIF-1alpha group, Ad group and NS group. After Ad-HIF-1alpha, Ad and NS were injected into the ischemic ventricle, expression of Ad-HIF-1alpha was observed and its therapeutic effect was evaluated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and neurological severity scores.


RESULTS
GFP expression distributed apart from the ventricle and reached a peak at 14 days and persisted for about 4 weeks under fluorescent microscope. The neurological severity scores was 2.4 +/- 0.5 at 24 h in Ad-HIF-1alpha group and there was no statistical significance compared with Ad group (2.6 +/- 0.5) and NS group (2.7 +/- 0.7) (P > 0.05). The scores were 1.6 +/- 0.7 at 48 h and 0.9 +/- 0.6 at 72 h in Ad-HIF-1alpha group, and there were statistical significance compared with Ad group (2.9 +/- 0.6 and 3.2 +/- 0.6 respectively) and NS group (3.0 +/- 0.7 and 3.2 +/- 0.8) (P < 0.05). The infarct volume was 81.2 mm(3) +/- 1.4 mm(3) at 72 h in Ad-HIF-1alpha group and there was statistical significance compared with Ad group (173.9 mm(3) +/- 1.3 mm(3)) and NS group (171.7 mm(3) +/- 6.2 mm(3)) (P < 0.05).


CONCLUSIONS
HIF-1alpha gene had definite therapeutic effect on focal cerebral ischemia in adult rats, which settles a foundation for next HIF-1alpha gene study and clinic application.
Tan
Xin-jie
XJ
Department of Neurology, Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400010, China.
Hu
Chang-lin
CL
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins