动物实验,脑白质损伤,γ-分泌酶抑制剂 z-bo 2020-08-22 584

　　Purpose: γ-secretase inhibitor (N-[N-(3,5-difluorophenylacetyl)-L-alanyl]-S-phenylglycine butyrate, DAPT) exposed to atmospheric pressure and high oxygen Investigate the effect on white matter damage in newborn mice at different concentrations.

　　Methods: The neonatal 3d mice were exposed to 48% and 80% hyperoxia and intraperitoneal DAPT (10 mg/kg) 1 hour before the hyperoxia exposure to establish a neonatal mouse idiopathic hyperoxic brain injury model . Mice were injected into the air control group (C), air + DAPT group (C + DAPT), hyperoxia group (H), and hyperoxia + DAPT group (H + DAPT). The brain mass and body weight of each group of mice were measured on the 3rd, 5th, 12th and 28th days. 48 hours after the model was established, the mouse brain tissue NICD mRNA (Notchintracellular domain) expression; G2 and MBP (myelin basic protein) expression were detected by RT-PCR; and the Morris water maze was performed on the 28th day.

　　Result: Compared with group C, the brain mass and body weight of mice in group H decreased significantly with age (P\u003c0.05). Compared with the H group, DAPT pretreatment was used in the hyperoxia exposure (after H + DAPT) group, and significantly increased the brain mass and body weight of the mice (P\u003c0.05). T-PCR showed that the expression of NICD mRNA was up-regulated after hyperoxia exposure, and DAPT could reverse the up-regulation of NICD in brain tissue induced by hyperoxia. Group NG2 cells increased and MBP cells decreased. Compared with H group, DAPT pretreatment (H + DAPT group) NG2 cells significantly decreased, and MBP cells increased significantly, both prolonged (P\u003c0.05)) and shortened The dwell time in the target quadrant (P\u003c0.05), and the number of virtual platforms passing through is reduced (P\u003c0.05). Compared with the H + DAPT group, the above indicators were significantly improved.

　　Conclusion: γ-secretase inhibitor (DAPT) inhibits the changes in brain Notch signal levels caused by hyperoxia exposure, reduces premature brain white matter damage caused by hyperoxia, and impairs long-term learning and memory damage caused by hyperoxia exposure.