The Expression Changes Of MMP-9 MRNA And Occludin MRNA In The Brain Of Neonatal Rats With Hypoxic-ischemic Brain Damage (HIBD)

ObjectiveIn this research the HIBD model was established to observe the expressions of MMP-9 mRNA and occludin mRNA. In order to investigate the mechanism of cerebral edema of neonatal rats induced by hypoxia-ischemia and provide an efficacious pathway for clinical therapy of neonatal HIE.Method1. Establishment of HIBD model:Neonatal 7-day-old Sprague Dawley(SD)rats were randomly.divided into sham-operation control group,HIBD3,6,24,48and72 h groups(n=6 per group). The model of HIBD was induced by unilateral carotid ligation,then exposed to hypoxic environment(8%O2,92%N2)for two hours. Sham-operation control group rats were only separated the left common carotid artery without being ligated, then were executed at 24 h after the operation. The behavior of the rats was observed during hypoxia.2. General examination of the brain:To observe the morphological changes of the ligated cerebral hemisphere.3. Expression of MMP-9 mRNA and occludin mRNA:The expressions of MMP-9 mRNA and occludin mRNA in the ligated cerebral hemisphere were measured by Real-time Q-PCR.Results1. Behavior of experimental animals:The behavior of all neonatal rats was normal before operation. Sham-operation control group had no abnormal behavior; Experiencing serious hypoxia,the rats of HIBD groups exhibited behavior problem.2. The morphological changes of the ligated cerebral hemisphere:The two cerebral hemispheres of sham group showed no pathological change. The ligated cerebral hemisphere of HIBD groups showed obvious pallor and edema at 24 h, liquefactive necrosis lesion at 72 h,or even cerebral hemisphere was completely liquefied with dural adhesions. 3. Expressions of MMP-9 mRNA and occludin mRNA①As compared to HIBD group,the expression of MMP-9 mRNA was lower in the sham-operation control group(0.7933±0.0859,P<0.05). After HIBD,it began to increase at 3 h(1.1533±0.1291),and peaked at 24 h(3.4883±0.1759,P<0.05 vs.the other group), maintained the high level at 72 h(1.6250±0.1157).②As compared to HIBD group,the expression of occludin mRNA was higher in the sham-operation control group(2.1780±0.0773,P<0.05). After HIBD, it began to decrease at 3 h(1.7186±0.1168),lowest at 24 h(0.9066±0.0602,P<0.05 vs.the other group),and maintained the low level at 72 h(1.5966±0.0799).③The expression of MMP-9 mRNA after HIBD negatively correlated with the expression of occludin mRNA(r=-0.815,P<0.05).Conclusions1. The HIBD model was successfully established.2. After HIBD,the expression of MMP-9 mRNA was increasd and the expression of occludin mRNA were decreased. They may play a role in the pathogenesis of HIBD in neonatal rats.3. After HIBD, the expression of MMP-9 mRNA negatively correlated with the expression of occludin mRNA, the decreased expression of occludin mRNA caused by the increased expression of MMP-9 mRNA may be an aspect of the mechanism of cerebral edema after HIBD.