南方医科大学学报

南方医科大学学报 ›› 2017, Vol. 37 ›› Issue (05): 600-.

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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

余军，赵维星，杜春彦，张娜，张卫东，晋圣阳，汪海，冯泽国   

  • 出版日期:2017-05-20 发布日期:2017-05-20

Choline improves lipopolysaccharide-induced central nervous system inflammatory response and cognitive dysfunction in mice

  • Online:2017-05-20 Published:2017-05-20

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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（P<0.05），胆碱预处理后穿台次数显著上升（P<0.05）；与对照组相比，LPS组小鼠海马IBA-1 蛋白（P<0.0001）、TNF-α（P<0.001）与IL-1β（P<0.01）明显升高，胆碱干预后明显降低IBA-1蛋白（P<0.05）和IL-1β（P<0.05）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（P<0.05），胆碱预处理后显著降低其磷酸化水平（P< 0.05）；胆碱干预组α7nAchR表达与其他3组相比显著增高（P<0.05）。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: Objective To assess the effect of choline in ameliorating lipopolysaccharide (LPS)-induced central nervous system inflammation and cognitive deficits in mice and explore the underlying mechanism. Methods Seventy-two mice were randomized into saline control group, LPS group, choline intervention group and choline control group. In the latter two groups, the mice received pretreatment with intraperitoneal injections of choline (40 mg/kg, 3 times daily for 3 consecutive days) prior to microinjection of LPS into the lateral cerebral ventricle to induce central nervous system inflammation; in saline and LPS groups, the mice were pretreated with saline in the same manner before intraventicular injection of artificial cerebrospinal fluid. Choline treatment was administered in the mice till the end of the experiment. The locomotor activity and spatial learning and memory capacity of the mice were examined. The expressions of Iba1 protein and proinflammatory cytokines (TNF-α and IL-β) I the hippocampal dentate gyrus, and the expressions of α7nAchR, p38 MAPK and phosphorylated p38 MAPK in the hippocampus of the mice were detected. Results Water maze test showed that compared with the saline control group, the mice in LPS group exhibited significantly reduced platform crossings (P<0.05), which was significantly increased by choline pretreatment (P<0.05). The mice pretreated with LPS expressed obviously increased levels of IBA-1 protein, TNF-α, and IL-1β in the hippocampus (P<0.01), and choline pretreatment significantly lowered the expressions of IBA-1 protein and IL-1β (P<0.05). The phosphorylation level of p38 MAPK increased significantly after LPS pretreatment (P< 0.05), and was reduced by choline pretreatment (P<0.05); α7nAchR expression increased significantly in choline intervention group as compared with that in the other 3 groups (P<0.05). Conclusion Choline can probably antagonize LPS-induced hippocampal p38 MAPK phosphorylation in mice via the α7nAchR signaling pathway to protective against LPS-induced neuroinflammation and cognitive impairment in mice.