摘要
目的探讨丰富环境对孕期阻塞性睡眠呼吸暂停低通气综合征(OSAHS)造成的小鼠认知功能损害和生长相关蛋白43(GAP-43)含量变化的影响及其相关炎症通路机制。方法实验组C57BL/6J小鼠孕第15天予以连续7 d间歇性缺氧环境,对应子鼠分别在第21天至2月龄放于丰富环境中饲养(OSAHS+EE组)和正常环境中饲养(OSAHS组)。对照组孕鼠置于正常氧气环境,对应子鼠在相同月龄期放于丰富环境饲养(Control+EE)和正常环境饲养(Control组)。在小鼠2月龄用Morris水迷宫评估空间学习记忆能力,用实时荧光定量PCR检测小鼠海马NF-κB、NLRP3和GAP-43 mRNA水平,Western blot检测海马NLRP3和GAP-43蛋白含量。结果与Control组比较,OSAHS组游泳路程增加(P<0.01),记忆期靶象限游泳路程百分比降低(P<0.01);海马NF-κB mRNA、NLRP3 mRNA和蛋白含量升高,GAP-43 mRNA和蛋白含量降低(P<0.01)。与Control组比较,OSAHS+EE组游泳路程、游泳路程百分比、NF-κB mRNA、NLRP3 mRNA和蛋白含量无明显差异。结论孕期OSAHS导致子代小鼠学习记忆能力受损和GAP-43蛋白水平降低,其机制可能与NF-κB/NLRP3水平升高有关,而丰富环境可改善这种损害。
Objective To investigate the effect of environmental enrichment on cognitive impairment and hippocampus GAP-43 changes induced by exposure to obstructive sleep apnea-hypopnea syndrome(OSAHS)during the period of late pregnancy in mice,and to explore relative inflammatory pathway mechanism.Methods The experimental group of C57BL/6J pregnant mice were exposed to an intermittent hypoxic environment for 7 consecutive days starting from gestational day 15.The corresponding offspring were then placed in an enriched environment from postnatal day 21 to 2 months of age(designated as OSAHS+EE group)or in a normal environment(designated as OSAHS group).Pregnant mice in the control group were maintained in a normal oxygen environment,and their corresponding offspring were placed in an enriched environment(designated as Control+EE group)or a normal environment(designated as Control group)at the same ages.The spatial learning and memory ability of the mice was assessed by Morris water maze at the age of 2 months.The mRNA levels of NF-kB,NLRP3 and GAP-43 in the hippocampus were detected by real-time fluorescence quantitative PCR,and the protein levels of NLRP3 and GAP-43 in the hippocampus were detected by Western blot.Results Compared with Control group,the swimming distance increased(P<0.01),and the percentage of swimming distance in target quadrant decreased(P<0.01)in OSAHS group.The level of NF-κB mRNA,NLRP3 mRNA and protein in the hippocampus was increased,and the level of GAP-43 mRNA and protein was decreased(P<0.01).Compared with the Control group,there were no significant differences in swimming distance,percentage of swimming distance,NF-κB mRNA,NLRP3 mRNA and protein content in the OSAHS+EE group.Conclusion OSAHS during pregnancy impairs the learning and memory ability of offspring mice and reduces the level of GAP-43 protein.The mechanism may be related to the increase of NF-κB/NLRP3 level,and environmental enrichment can improve the damage.
作者
程云舟
厉雪艳
张月明
危如梦
王杨
Cheng Yunzhou;Li Xueyan;Zhang Yueming;Wei Rumeng;Wang Yang(Dept of Pediatrics,The Affiliated Chaohu Hospital of Anhui Medical University,Hefei 238000;Dept of Sleep Disorders,The Affiliated Chaohu Hospital of Anhui Medical University,Hefei 238000;Dept of Neonatology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)
出处
《安徽医科大学学报》
北大核心
2025年第7期1212-1217,共6页
Acta Universitatis Medicinalis Anhui
基金
安徽省高等学校科研计划项目(编号:2022AH050759)。
