| Objective:To investigate whether vitamin A (VA) can activate PI3K/Akt signaling pathway to decrease primary neurons apoptosis caused by hypoxic-ischemic brain damage (HIBD).Methods:The gestational VA deficiency model of rats was built according to the conventional method in our group, and 7-day-old Wistar rats were damaged by HIBD using the classcial method of Rice. The hippocampus tissue were collected at 1,3,7 and 14 days following HIBD. Primary neurons of neonatal rats cultured in vitro were injured by oxygen and glucose deprivation (OGD) following retinoic acid (RA) treatment, and observed cell morphological changes on an inverted microscopy. Meanwhile, the primary neurons injured OGD were infected by si/Ad-RARa adenovirus, the levels of RARa, PI3K, Akt, Bad expressions and p-Akt, p-Bad phosphorylation in the different treatment groups were determined by Real-time PCR and Western blots.Results:After HIBD for 3-7 days, the levels of RARα、PI3K、Akt mRNA expressions and RARa、PI3K、p-Akt、p-Bad protein expressions in the VAN group were all significantly higher than those of the VAD group (P<0.05). The cell morphology of the OGD primary neurons treated by RA were better than those of neurons injured by OGD without RA treatment. Furthermore, the levels of RARa, PI3K, Akt as well as p-Bad expressions were statistically increased in the OGD with RA group (P<.05). After OGD injured the primary neurons infected by si/Ad-RARa adenovirus, the expression levels of PI3K, Akt and the phosphorylation levels of Akt, Bad were decreased or increased significantly with the changes of RARa expression levels (P<0.05). However, the levels of total Bad mRNA and protein expressions were no significant differences among the various groups.Conclusion:Vitamin A suppresses neurons apoptosis injured by HIBD, and its mechanism is that VA modultes PI3K/Akt signaling pathway and up-regulates the phosphorylation level of Bad to protect neurons induced by HIBD from apoptosis via RARa. |
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