肌醇磷酸酶-1与宫内感染小鼠海马神经炎性反应引起认知障碍的关系  

The relationship between inositol phosphatase - 1 and cognitive impairment induced by hippocampal neuritis in intrauterine infected mice

作　　者：李多多[1] 程远[2] 李振晓 朱凤莲[1] Li Duoduo;Cheng Yuan;Li Zhenxiao;Zhu Fenglian(the Third Ward, Department of Pediatrics, the First A fdiated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China;Department of Physiology and Neurobiology ,Xinxiang Medical University,Xinxiang 453003 ,Henan Province, China)

机构地区：[1]新乡医学院第一附属医院小儿内科三病区,河南卫辉453100 [2]新乡医学院生理学与神经生物学教研室,453003

出　　处：《中华实用儿科临床杂志》2018年第11期850-853,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金（81501265）;河南省教育厅科学技术研究重点项目（148320002,17A310024）;新乡医学院第一附属医院科研培育基金（py2014014）

摘　　要：目的探讨肌醇磷酸酶-1（SHIP-1）与宫内感染小鼠海马神经炎性反应引起认知障碍之间的关系。方法30只C57BL/6雌鼠与15只雄鼠以21合笼，孕鼠均分为宫内感染模型组脂多糖（LPS组）和对照组，LPS组于孕13.5 d尾静脉注射LPS 350 μg/kg制备宫内感染模型，对照组注射等量9 g/L盐水。孕鼠产后3 d，各组分别取15只新生鼠处死，分离海马组织提取蛋白，采用Western blot法检测海马组织中SHIP-1、核因子-κB（NF-κB）p65、NF-κB磷酸化（NF-κBp）的蛋白水平，采用酶联免疫吸附（ELISA）法检测海马组织中白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的水平。待剩余小鼠8周龄时（各15只），行Morris水迷宫实验、定位航行和空间探索实验，评估小鼠是否存在认知障碍。结果对照组小鼠海马组织中SHIP-1蛋白表达（0.677±0.074）明显高于LPS组（0.317±0.095），而NF-κB p65及NF-κBp蛋白表达（0.630±0.109、0.352±0.084）则明显低于LPS组（1.028±0.029、1.080±0.113），差异均有统计学意义（t=2.984、3.516、5.161，P=0.041、0.025、0.007）；LPS组海马组织中炎性因子IL-1β和TNF-α的表达[（5.875±0.349） pg/mg、（14.256±0.784） pg/mg]明显高于对照组[（1.621±0.151） pg/mg、（3.984±0.255） pg/mg]，差异均有统计学意义（t=11.190、12.460，P=0.000、0.000）。LPS组小鼠学习能力[逃避潜伏期1～6 d分别为（58.286±1.418） s、（56.036±2.252） s、（55.071±1.856） s、（50.071±3.251） s、（52.893±2.372） s、（46.929±3.761） s]明显高于对照组[逃避潜伏期1～6 d分别为（53.679±2.413） s、（47.571±3.529） s、（54.071±2.777） s、（47.250±2.864） s、（45.107±3.447） s、（42.393±3.463） s]，差异有统计学意义（F=4.466，P=0.001）。空间探索实验结果：LPS组在第1次进入平台SE象限的潜伏时间[（44.080±6.313） s]明显长于对照组[（25.900±6.033） s]，而停留在平�Objective To investigate the relationship between cognitive impairment and SH2 domain-containing inositol phosphatase-1（SHIP-1）induced by hippocampal neuritis in intrauterine infected mice.MethodsThirty C57BL/6 female mice and 15 male mice were caged in a ratio of 21.After that, the pregnant mice were divided into 2 groups.A mice model of intrauterine infection was established that intrauterine infection group （lipopolysaccharides, LPS group） induced by LPS at the concentration of 350 μg/kg and control group treated with same volume of saline（9 g/L）. At 3 days postpartum, 15 mice in each group were killed for hippocampus, and the protein levels of SHIP-1, nuclear factor-κB（NF-κB） p65 and phosphorus NF-κB（NF-κBp） in the hippocampus of the newborn mice were detected by Western blott, while the levels of interleukin 1β（IL-1β） and tumor necrosis factor （TNF-α）were detected by using enzyme linked immunosoobent assay.When the remaining mice were 8 weeks old（10 in each group）, Morris water maze experiments were performed respectively, which the mice were tested for evaluating learning and memory function by positioning navigation and space exploration experiments.ResultsThe expression of SHIP-1 was significantly increased in control group（0.677±0.074） compared with LPS group（0.317±0.095, t=2.984, P=0.041）, while the levels of NF-κB p65, and NF-κBp, were significantly lower in control group（0.630±0.109, 0.352±0.084） than LPS group（0.630±0.109, 0.352±0.084）（t=3.516, 5.161, P=0.025, 0.007）. Moreover, LPS significantly enhanced the expression of IL-1β and TNF-α[（5.875±0.349） pg/mg, （14.256±0.784） pg/mg] compared with control group[（1.621±0.151） pg/mg, （3.984±0.255） pg/mg], and the differences were significant（t=11.190, 12.460, P=0.000, 0.000）. By the average Escape Latency tests for 6 days, LPS group [at 1-6 days （58.286±1.418） s, （56.036±2.252） s, （55.071±1.856） s, （50.071±3.251） s, （52.893±2.372） s, �

关 键 词：宫内感染 肌醇磷酸酶-1 认知障碍 

分 类 号：R722.12[医药卫生—儿科]