The Neuroprotective Effects of Xenon on Neonatal Rats with White Matter Damage by Regulating Expression of microRNA-210 and HIF-1αThe Neuroprotective Effects of Xenon on Neonatal Rats with White Matter Damage by Regulating Expression of microRNA-210 and HIF-1α

Abstract Background:Premature infant is a significant health care burden. White matter damage (WMD) is a leading cause of acute mortality and chronic morbidity in preterm. Xenon (Xe) intervention was given to the 3-day-old neonatal rats with brain white matter injury. By detecting the changes in the expression level of microRNA210 and hypoxia inducible factor 1α (HIF-1α) in brain tissue before and after xenon intervention, we can research the molecular basis and the mechanism of neuroprotective on effect of xenon on brain white matter damage in neonatal rats.Methods:Three-day-old SD rats were randomly divided into sham group(Group A, n=24), lipopolysaccharide(LPS)+hypoxia-ischemia(HI) group (Group B, n=24) and LPS+HI+Xe group ( n=72). The onset of Xe inhalation started at 0,2 and 5 hours in subgroups C,D,and E respectively.We investigated the neurobehavioral deficits by performing TUNEL and hematoxylin and eosin (HE) staining and examining the expression of miR-210and HIF-1α in brain tissues via RT-PCR and western blot. Results: Xe treatment improved the histological alterations and decreased the number of apoptotic cells in group C pups.Compared to group A,Detection of miR-210 level by RT-PCR. the expression level of miR-210 in neonatal rats' periventricular tissue increased significantly at all time points in group B (p<0.05).While the expression level of miR-210 in brain tissues of group B was significantly lower at 48h and 72h than that of group C(p<0.05).Similarly,Detection of HIF-1α protein by Western blot. The level of HIF-1α protein in group B brain tissues was significantly higher than that of group A at each time point (p<0.05), Xe treatment resulted in a marked increase in HIF-1α in C,D, and E subgroups (P < 0.05, compared to group B).Conclusions: These results demonstrate that the expression of HIF-1α and miR-210 increased in periventricular tissues and Xe could relieve the white matter damage by up-regulating the expression of HIF-1α and its target gene miR-210.The Xe therapeutic time window was within 5 hours after intervention, the sooner the better.