γ-分泌酶抑制剂 z-bo 2020-11-11 365

　　Objective: To investigate the effects of γ-secretase inhibitor (N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, DAPT) on the brain of newborn mice exposed to atmospheric pressure and high concentration oxygen The role of white matter damage.

　　Methods: Newborn 3-day mice were exposed to 80% hyperoxia for 48 hours to establish an immature hyperoxia brain injury model in newborn mice, and intraperitoneal injection of DAPT (10 mg/kg) 1 h before hyperoxia exposure, the mice Divided into air control group (C), air + DAPT group (C+DAPT), hyperoxia group (H), hyperoxia + DAPT group (H+DAPT). Detect the brain mass and body mass of mice in each group on 3, 5, 12 and 28 days; RT-PCR detects the expression of NICDmRNA (Notch intracellular domain) in the brain tissue of mice 48 h after the model is made; immunohistochemical detection on day 12 NG2 and MBP (myelin basic protein) expression; Morris water maze on 28th day to evaluate the learning and memory ability of mice in each group.

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

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