胆碱改善脂多糖诱导的小鼠中枢神经系统炎症反应及认知功能障碍
发布时间：2018-10-25 20:55
【摘要】：目的观察胆碱对脂多糖(LPS)诱导的中枢神经系统(CNS)炎症反应及认知损伤的影响,并对其作用机制进行分析。方法采用侧脑室注射LPS建立小鼠CNS炎症模型,随机分为生理盐水对照组、LPS组、LPS+胆碱40 mg/kg组、胆碱40 mg/kg组4组。药物干预组和药物对照组胆碱预处理3 d,下午12、2和4 pm各1次腹腔注射,对照组和LPS组生理盐水预处理3 d(时间次数同上),胆碱给药贯穿整个实验。观察小鼠自发活动,测定小鼠空间学习和记忆能力。检测海马齿状回IBA-1蛋白表达情况,测定海马TNF-α、IL-1β水平,分析海马α7nAchR、MAPK p38蛋白和磷酸化p38蛋白表达情况。结果与对照组相比,LPS组小鼠在水迷宫测试中穿台次数明显减少(P0.05),胆碱预处理后穿台次数显著上升(P0.05);与对照组相比,LPS组小鼠海马IBA-1蛋白(P0.0001)、TNF-α(P0.001)与IL-1β(P0.01)明显升高,胆碱干预后明显降低IBA-1蛋白(P0.05)和IL-1β(P0.05)的升高,部分抑制TNF-α的升高;LPS处理后p38MAPK磷酸化水平明显升高(P0.05),胆碱预处理后显著降低其磷酸化水平(P0.05);胆碱干预组α7nAchR表达与其他3组相比显著增高(P0.05)。结论胆碱可能通过激活αnAchR来抑制LPS诱导的小鼠海马p38MAPK磷酸化,对LPS诱导的CNS炎症以及认知功能障碍的小鼠具有保护效应。
[Abstract]:Aim to observe the effect of choline on the inflammatory response and cognitive impairment of central nervous system (CNS) induced by lipopolysaccharide (LPS), and to analyze its mechanism. Methods the inflammatory model of CNS was established by intracerebroventricular injection of LPS in mice. The mice were randomly divided into four groups: normal saline control group, LPS 40 mg/kg group and choline 40 mg/kg group. The drug intervention group and the drug control group were pretreated with choline for 3 days, then injected intraperitoneally for 12 minutes and 4 pm respectively. The control group and the LPS group were pretreated with normal saline for 3 days (the time was the same). Choline administration ran through the whole experiment. The spontaneous activity of mice was observed and the ability of spatial learning and memory was measured. The expression of IBA-1 protein in dentate gyrus and the levels of TNF- 伪 and IL-1 尾 in hippocampus were detected, and the expression of 伪 7nAchRmMAPK p38 protein and phosphorylated p38 protein in hippocampus were analyzed. Results compared with the control group, the number of platform piercing was significantly decreased in LPS group (P0.05), and increased significantly after choline pretreatment (P0.05). Compared with the control group, IBA-1 protein (P0.0001), TNF- 伪 (P0.001) and IL-1 尾 (P0.01) were significantly increased in LPS group. The levels of IBA-1 protein (P0.05) and IL-1 尾 (P0.05) were significantly decreased after choline treatment, and the increase of TNF- 伪 was partly inhibited. After LPS treatment, p38MAPK phosphorylation level increased significantly (P0.05), choline pretreatment significantly decreased its phosphorylation level (P0.05); choline intervention group 伪 7nAchR expression was significantly higher than the other three groups (P0.05). Conclusion choline may inhibit p38MAPK phosphorylation in hippocampus of mice induced by LPS by activating 伪 nAchR, and has protective effect on CNS inflammation induced by LPS and cognitive impairment in mice.
【作者单位】： 解放军总医院麻醉手术中心;中国医学科学院北京协和医学院;军事医学科学院卫生学环境医学研究所心血管药物研究中心;
【基金】：军队保健专项课题(15BJZ36) 军队医药卫生十二五重大专项课题(AWS11J003)
【分类号】：R741
，
本文编号：2294813
[Abstract]:Aim to observe the effect of choline on the inflammatory response and cognitive impairment of central nervous system (CNS) induced by lipopolysaccharide (LPS), and to analyze its mechanism. Methods the inflammatory model of CNS was established by intracerebroventricular injection of LPS in mice. The mice were randomly divided into four groups: normal saline control group, LPS 40 mg/kg group and choline 40 mg/kg group. The drug intervention group and the drug control group were pretreated with choline for 3 days, then injected intraperitoneally for 12 minutes and 4 pm respectively. The control group and the LPS group were pretreated with normal saline for 3 days (the time was the same). Choline administration ran through the whole experiment. The spontaneous activity of mice was observed and the ability of spatial learning and memory was measured. The expression of IBA-1 protein in dentate gyrus and the levels of TNF- 伪 and IL-1 尾 in hippocampus were detected, and the expression of 伪 7nAchRmMAPK p38 protein and phosphorylated p38 protein in hippocampus were analyzed. Results compared with the control group, the number of platform piercing was significantly decreased in LPS group (P0.05), and increased significantly after choline pretreatment (P0.05). Compared with the control group, IBA-1 protein (P0.0001), TNF- 伪 (P0.001) and IL-1 尾 (P0.01) were significantly increased in LPS group. The levels of IBA-1 protein (P0.05) and IL-1 尾 (P0.05) were significantly decreased after choline treatment, and the increase of TNF- 伪 was partly inhibited. After LPS treatment, p38MAPK phosphorylation level increased significantly (P0.05), choline pretreatment significantly decreased its phosphorylation level (P0.05); choline intervention group 伪 7nAchR expression was significantly higher than the other three groups (P0.05). Conclusion choline may inhibit p38MAPK phosphorylation in hippocampus of mice induced by LPS by activating 伪 nAchR, and has protective effect on CNS inflammation induced by LPS and cognitive impairment in mice.
【作者单位】： 解放军总医院麻醉手术中心;中国医学科学院北京协和医学院;军事医学科学院卫生学环境医学研究所心血管药物研究中心;
【基金】：军队保健专项课题(15BJZ36) 军队医药卫生十二五重大专项课题(AWS11J003)
【分类号】：R741
，
本文编号：2294813
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