| Objective:Neonatal hypoxic ischemic encephalopathy (HIE) is caused by perinatal asphyxia and anoxia of nervous system damage, is one of the most common disease of the newborn. It is the important reasons of permanent neurological dysfunction for infants and young children even of neonatal death. Clinical drug therapy are little effective at the present stage. The purpose of this paper is successfully established with the newborn rat hypoxic ischemic brain damage (HIBD) animal model, after that to give systemic mild hypothermia therapy immediately. To detect expression of Bax mRNA and HIF-la mRNA in the newborn rat brain tissue at different time points different groups and explore the relationship between the both. Trying to clarify possible mechanism of neuroprotection of mild hypothermia therapy of HIBD, and provide the new clinical treatment ideas of neonatal HIE.Methods:A total of120female or male SD rats aged7d, and using the stochastic method randomly divided into three groups:sham operation group(A group), normal group(B group), mild hypothermia group(C group), each group has40rats(n=40in each group). B group and C group must prepare HIBD animal model at first. According to the experiment demands that the time of death was divided into five subgroups:2h,6h,12h,24h,48h group, each subgroup has8rats(n=8in each subgroup). To prepare HIBD animal model, B group and C group were prepared by ligation of left common carotid operation, after that rats were placed into hypoxic environment of8%O2+92%NO2concentration for2hour. Observe behavior of neonatal rats in the process. The mild hypothermia treatment was given immediately in C group after HIBD. Depending to the experiment request each experimental group was killed by beheaded method to collect brain tissue. Observe brain tissue in morphological changes. By using the real-time fluorescent quantitative PCR method (real-time CR method), we can detected the expression changes of Bax and HIF-la gene in brain tissue on the left side of each group rats. Recorded the statistics data and analyzed with associated statistic methods.Results:(1) Neonatal rats before and after HIBD appeared various abnormal activities.(2) Brain tissue of neonatal rats in B group appeared edema by macroscopic observation at different time points, but there were normal morphology of brain tissue of rats in C group.(3) Bax mRNA expression:Neonatal rats in A group each time point had little expression, expression in B group raised at2h, reach peak atl2h,12h--48h remains high peak, but C group2h decline and reach the lowest level at6h, but the late slightly increased that12h-48h after mild hypothemia, expression of Bax gene microliter.(4) HIF-la mRNA expression:In A group the expression of HIF-lα mRNA was minimal, expression raised at2h and increased gradually, reach the highest at48h in B group; in C group expression of HIF-lα mRNA slightly increase at2h, and later decreased gradually.Conclusions:(1) Mild hypothermia can reduce changes of edema tissue of neonatal rats after HIBD, to prompt the mild hypothermia of newborn rat after HIBD may play a protective role of the nervous system.(2) Mild hypothermia could inhibit expression of Bax mRNA; reduce tissue pathological damage process of HIBD, thus inhibiting nerve cell apoptosis.(3) Expression of HIF-la mRNA slightly raises downstream Bax mRNA in the late of mild temperature treatment. Thereby eliminate apoptotic cells in the course of HIBD, which effect possible mechanism of neuroprotection. These offers a new clinical thought and method for neonatal HIE. |
