南方医科大学学报2017，Vol.37Issue(5)：600-606,7.DOI:10.3969/j.issn.1673-4254.2017.05.06
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
Choline improves lipopolysaccharide-induced central nervous system inflammatory response and cognitive dysfunction in mice
摘要
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.关键词
胆碱/脂多糖/中枢神经系统炎症/p38MAPK/α7nAchRKey words
choline/lipopolysaccharide/neuroinflammation/p38 MAPK/α7nAchR引用本文复制引用
余军,赵维星,杜春彦,张娜,张卫东,晋圣阳,汪海,冯泽国..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[J].南方医科大学学报,2017,37(5):600-606,7.基金项目
军队保健专项课题(15BJZ36) （15BJZ36）
军队医药卫生十二五重大专项课题(AWS11J003) （AWS11J003）
