动物造模 z-bio 2023-02-04 696

　　Objective: To investigate the effect of γ-secretase inhibitor on white matter damage in neonatal mice induced by atmospheric pressure and high concentration oxygen exposure.

　　METHODS: Neonatal mice were exposed to 80% hyperoxia for 48 hours to establish an immature hyperoxic brain injury model in neonatal mice, and DAPT (10 mg/kg) was injected intraperitoneally 1 hour before hyperoxia exposure. Divided into air control group (C), air+DAPT group (C+DAPT), hyperoxia group (H), hyperoxia+DAPT group (H+DAPT). The brain weight and body weight of the mice in each group were detected on the 3rd, 5th, 12th and 28th days; the expression of NICDmRNA (Notch intracellular domain) in the brain tissue of the mice was detected by RT-PCR 48 hours after the model was made; the expression of NICDmRNA (Notch intracellular domain) in the mouse brain tissue was detected on the 12th day; immunohistochemical detection on the 12th day The expression of NG2 and MBP (myelin basic protein); the Morris water maze on the 28th day to evaluate the learning and memory ability of the mice in each group.

　　Results: Compared with group C, the brain weight and body weight of mice in group H decreased significantly with age (P<0.05); compared with group H, DAPT pretreated with hyperoxia exposure (group H+DAPT) The brain weight and body weight of mice increased significantly (P<0.05); RT-PCR indicated that the expression of NICD mRNA was up-regulated after hyperoxia exposure, and DAPT could reverse the up-regulation of NICD in brain tissue caused by hyperoxia; immunofluorescence double-labeling showed that NG2 in group H was up-regulated. Compared with group H, NG2 cells were significantly reduced and MBP cells were significantly increased after DAPT pretreatment (H+DAPT group); compared with group C, the escape latency and swimming distance of Morris water maze group H were prolonged. (P<0.05), the residence time in the target quadrant was shortened (P<0.05), and the number of crossing the virtual platform was reduced (P<0.05).

　　Conclusion: γ-secretase inhibitor (DAPT) can inhibit the changes of Notch signal level in the brain induced by hyperoxia exposure, reduce the damage of immature white matter induced by hyperoxia, and reduce the damage of long-term learning and memory ability caused by hyperoxia exposure in the neonatal period.