Research On The Expression Of HIF-1α And TfR MRNA And Their Relationship In Rat Models With Hypoxic-ischemic Periventricular Lerkomalacia

ObjectiveTo establish Hypoxic-ischemic PVL animal model of the4day-old SD rat, onthis condition, to do the research on the expression of HIF-1α and TfR mRNA andtheir correlation, to provide the theoretical bases of cerebral Hypoxic-ischemiainjury’s pathogenesis and mechanism of iron metabolic in brain.Methods1. The4day-old SD rats were randomly divided into a control group and a PVLgroup according to the random number table.The PVL group was subjected tobilateral common carotid arteries ligation and then they were put into a box filled withhypoxic air.The control group was subjected to sham surgery and was exposed tonormoxic air during the experiment.HE staining was used to observe the brainpathological changes, Western blot method to investigate the expression of MBP.Inspections were made for maturation of physical characteristics such as weight, eyeopening time. Motor function test were carried after surgery.2. SD rats divided into4groups:a control and HIF-1αgroup, a control and blankgroup，PVL and HIF-1αcontrol group, PVL and PBS group. And another4groups: acontrol and PBS group, a control and HIF-1αcontrol group，PVL and HIF-1αcontrolgroup, PVL and PBS group.The expression of HIF-1αand TfR mRNA wasinvestigated by Western blot method and Real-time PCR analysis respectively．Results1. After operation, the weight of PVL group was lighter than that of the controlgroup.The mean value of eye opening time in the PVL group was significantlydelayed compared with the control group. For the motor function tests, the PVL groupshowed shorter hanging time in hanging test and weaker ability of cliff eacaping. The Morris water maze test showed that the rats of model groups had spatial learning andmemory cognition defect. The difference was statistically significant.2. The white matter showed rarefaction, liquefaction and microglia hyperplasia by HEstaining for the PVL group.3. The expression of MBP was significantly decreased in the PVL group after HI oneweek compared with the control group.4. The PVL and PBS group, compared with the control and blank group，had higherexpression level of HIF-1α by Western blot analysis. So did the expression of TfRmRNA investigated by Real-time PCR analysis.5. The control and HIF-1αgroup compared with the control and blank group. Theresults showed that HIF-1αwas increased for the first group by Western blot analysis.So did the expression level of TfR mRNA by Real-time PCR analysis.6. The expression level of HIF-1αfor the PVL and PBS group was higher than thePVL and HIF-1αcontrol group by Western blot anaysis. So did the expression levelof TfR mRNA by Real-time PCR analysis.Conclusions1. We have set up the PVL model for4day-old neonatal rat successfully by theligation of common carotid artery bilaterally plus hypoxia. It was similar to humanpreterms for pathology.2. The expression level of HIF-1αwas increased in the hypoxic-ischemic PVL model.The expression level of TfR mRNA also increased.3. In PVL model, the decreasing of HIF-1α would decrease the expression of TfRmRNA. The increasing of HIF-1αwould increase the expression of TfR mRNA.4. The increasing expression of TfR mRNA induced the change of Fe. It may be apossible mechanism of iron metabolic disorders when hypoxic-ischemic. Owing tothe complexity of brain iron homeostasis,the mechanism between HIF-1α and TfRmRNA in brain should be further researched．...