Preliminary study on the short－term and long－term effects of the inhibition of hypoxia inducible factor－1 alpha decomposition and activation of Wnt signaling pathway in brain injury in neonatal rats / 中国新生儿科杂志

ABSTRACT

Objective To investigate the protective effect of inhibition of hypoxia inducible factor－1 alpha (HIF－1α) and activation of Wnt signaling pathway on brain injury in neonatal rats.Method A total of 312 newborn SD rats were used to establish cerebral white matter damage model (WMD) on day 3.And they were randomly assigned into the model group (WMD group), post－modeling HIF－1αdecomposition inhibition group (PHI group), and post－modeling HIF－1αdecomposition inhibition with activation of Wnt signaling pathway group (PHI+activated Wnt group ) and post－modeling HIF－1αdecomposition inhibition with inhibition of the Wnt signaling pathway group (PHI+inhibition Wnt group).Brain tissues were taken on day 1, 3, 7 and 14 after modeling, respectively.The changes of oligodendrocyte precursor cell (OPC) and oligodendrocyte ( OL ) in brain tissues at different time points were observed by tissue immunofluorescence.The expression of HIF－1αprotein in the brain tissue of each time point was measured by western blot technique.The mRNA level of HIF－1αand Wnt7a in the brain tissue of each time point was detected by RT－qPCR technique.Behaviors of rats were tested by the suspension experiment , the open field experiment and the dark experiment , at 28 d after modeling.Result The numbers of OPC on 1 d and 3 d after modeling and the number of OL on 7 d and 14 d after modeling in PHI +activated Wnt group were significantly higher than the other three groups.The content of HIF－1αin WMD group was the least on 1, 3, 7 and 14 d, but the content of PHI+activated Wnt group was the highest , and the difference was statistically significant (P＜0.05).On 1, 3, 7 and 14 d after modeling, the expression level of HIF－1αand Wnt7a in PHI+activated Wnt group were higher than those in the other three groups , the difference was statistically significant (P＜0.05), and Wnt7a expression was positively correlated with the change of HIF－1α(P＜0.05).There was no significant difference of suspension experiment at 28 d after modeling between groups. Compared with other groups , WMD group had the lowest score on open field experiment ( P＜0.05).The PHI+activation Wnt group had better memory function , and then the PHI group , WMD group.The latent time of dark experiment were significantly shorter in PHI +acitivation Wnt group.There were more mistaken time of dark experiment in WMD group compared with PHI +activation Wnt group.Conclusion Inhibition of HIF－1αdecomposition and activation of Wnt signaling pathway have partially repair effect on brain injury in neonatal rats.