Abstract:

Objective To investigate the effects of dexmedetomidine on oxidative stress and inflammation in prostaglandin induced asphyxiated offspring by activating PI3K/AKT signal pathway and explore the mechanism of brain protection as well. Methods Pregnant rats were randomly grouped into model group，dexmedetomidine low⁃dose group，dexmedetomidine high⁃dose group，and dexmedetomidine + LY294002 group，the pregnant rats in the control group gave birth naturally，while the pregnant rats in the model group and the drug administration group were used to construct the asphyxia model of labor. After grouping，12 offspring rats were selected from each group to detect their learning and memory abilities，hippocampal neuron damage and apoptosis，levels of superoxide dismutase（SOD），malondialdehyde（MDA），cyclooxygenase⁃2（COX⁃2）and interleukin⁃6（IL⁃6）in the brain tissue，expression of autophagy and PI3K/AKT pathway⁃related proteins in brain tissue. Results Compared with the control group，the hippocampal neurons of offspring rats in the model group were severely damaged. The apoptosis rate，levels of MDA，COX⁃2 and IL⁃6 in brain tissue，and expression levels of LC3⁃II/LC3⁃I，Beclin⁃1 and P62 were obviously increased（P < 0.05），residence time in the target quadrant，times of crossing the original platform， number of neurons，and levels of SOD and p⁃PI3K/PI3K and p⁃Akt/Akt in the brain tissue were obviously decreased（P < 0.05）. Compared with the model group，the damage of hippocampal neurons in the dexmedetomidine groups were alleviated. The apoptosis rate，levels of MDA，COX⁃2 and IL⁃6 in brain tissue，and expression levels of LC3⁃ Ⅱ/LC3⁃Ⅰ，Beclin ⁃1 and P62 were all decreased（P < 0.05），residence time in the target quadrant，times of crossing the original platform，number of neurons，and levels of SOD and p⁃PI3K/PI3K and p⁃Akt/Akt in brain tissue were all increased（P < 0.05），and high ⁃ dose dexmedetomidine had an even stronger effect. In addition， compared with the high⁃dose dexmedetomidine group，the trend of various indexes in dexmedetomidine + LY294002 group was reversed. Conclusion Dexmedetomidine can reduce prostaglandin⁃induced oxidative stress and inflam⁃ mation，inhibit autophagy，reduce hippocampal neuron damage and apoptosis，and improve learning and memory functions of labor asphyxia neonatal offspring rats by activating PI3K/AKT signaling，and thus it plays a role in brain protection.

Key words:

phosphatidylinositol 3?kinase/protein kinase B, autophagy, dexmedetomidine, prosta? glandins, labor asphyxia, brain protection