[Relationship between hypoxia inducible factor 1alpha: expression and neuron apoptosis during hypoxia ischemia brain damage in neonatal rats].
OBJECTIVE
To investigate the relationship between the expression of hypoxia inducible factor la (HIF-1alpha) and the neuron apoptosis during a hypoxia ischemia brain damage and explore the role of HIF-1alpha in regulating the neuron apoptosis and repairing the brain damaged by hypoxia and ischemia.


METHODS
Forty SD rats aged 10 days were randomly divided into the experiment group and the control group, with 20 rats in each group. In the experimental group, the rats were anesthetized with ethylether. The right common carotid artery was exposed and ligated. Then, they were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2.5 hours. In the control group, the right common carotid artery was exposed but was not ligated or exposed to hypoxia. The brain tissues were harvested from the rats in the both groups at 4, 8, 24, 48 and 72 hours after the hypoxia and ischemia, and from the rats in the control group at the same time points. The HIF-1alpha protein expression and the cleaved caspase 3 (CC3) protein expression were detected with the immunohistochemistry method. The apoptosis cells were detected with the TUNEL staining method.


RESULTS
In the experimental group, the HIF-1alpha expression was significantly increased at 4 hours after operation, at the peak level at 8 hours, and began to decrease at 24 hours. The CC3 protein was expressed at 4 hours after operation, and was slightly expressed at 8 hours, but was significantly increased at 24 hours; the higher levels were maintained at 48 and 72 hours. However, in the control group, both the expression levels of HIF-1alpha and the CC3 protein were extremely low. So, the expression levels of HIF-1alpha and the CC3 protein were significantly higher in the experimental group than in the control group (P < 0.01). The TUNEL staining showed that in the experimental group the positive cells were significantly increased after the hypoxia and ischemia, with a peak level at 72 hours after the hypoxia and ischemia; however, in the control group there were few positive cells. TUNEL positive cells in the experimental group were significantly more than that in the control group (P < 0.01).


CONCLUSIONS
The expression tendency of HIF-1alpha is completely different from that of CC3. HIF-1alpha may have a protective role in regulating the neuron apoptosis in the neonatal hypoxia-ischemia brain damage and may promote the repairing and rebuilding process in the brain that was damaged by hypoxia and ischemia.
Li
Lihua
L
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu Sichuan, 610041, PR China. llhua9@163.com
Qu
Yi
Y
Mao
Meng
M
D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries; D053148:Caspase 3 / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053148:Caspase 3