氯马斯汀诱导海马髓鞘再生对脓毒症相关性脑病模型小鼠认知功能损伤的影响  

Effect of chlorpheniramine-induced hippocampal myelin regeneration on cognitive dysfunction in a sepsis-associated encephalopathy mouse model

作　　者：简家雄 殷晓宇 高炟鹏 沈锦春 JIAN Jiaxiong;YIN Xiaoyu;GAO Dapeng;SHEN Jinchun∗(Department of Anesthesiology,Affiliated Jinling Hospital,Medical School of Nanjing University,Nanjing,Jiangsu 210002,China)

机构地区：[1]南京大学医学院附属金陵医院麻醉科,江苏南京210002

出　　处：《徐州医科大学学报》2025年第3期157-163,共7页Journal of Xuzhou Medical University

基　　金：江苏省自然科学基金(BK20242097)。

摘　　要：目的探究氯马斯汀(CLE)对脓毒症相关性脑病(SAE)模型小鼠认知功能损伤的改善作用及机制。方法选择8周龄C57BL/6雄性小鼠40只,按照随机对照原则将实验动物分为对照组、CLE组、脂多糖(LPS)组、LPS+CLE组,每组10只。LPS+CLE组和CLE组连续14 d腹腔注射10 mg·kg-1·d-1氯马斯汀并分别在第7天注射5 mg/kg的脂多糖或等体积生理盐水,LPS组和对照组连续14 d腹腔注射等体积溶剂并分别在第7天注射5 mg/kg的脂多糖或等体积的生理盐水。使用旷场实验、新物体识别实验、Y迷宫实验检测小鼠行为学变化。采用Western blot检测小鼠海马白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)及髓鞘碱性蛋白(MBP)表达水平,免疫荧光法检测小鼠海马小胶质细胞数量、MBP及c-fos阳性神经元表达情况。结果与对照组相比,LPS组小鼠旷场实验中总路程及中心区时间的差异均无统计学意义(P>0.05),新物体识别实验辨别指数及Y迷宫实验自发交替率下降,IL-6、IL-1β表达水平及小胶质细胞数量升高,MBP表达水平下降及c-fos阳性神经元数目减少,差异有统计学意义(P<0.05);与LPS组相比,LPS+CLE组小鼠旷场实验相关指标的差异无统计学意义(P>0.05),新物体识别实验辨别指数、Y迷宫实验自发交替率、MBP表达水平及c-fos阳性神经元数目均明显升高,差异有统计学意义(P<0.05)。结论氯马斯汀可能通过诱导海马髓鞘再生,增加活动相关性神经元数量,改善SAE模型小鼠认知功能损伤。Objective To explore the improvement effect and mechanism of chlorpheniramine(CLE)on cognitive dysfunction in a sepsis-associated encephalopathy(SAE)mouse model.Methods Forty 8-week-old male C57BL/6 mice were randomly divided into four groups(n=10):Control group,CLE group,Lipopolysaccharide(LPS)group,and LPS+CLE group.The LPS+CLE group and CLE group were intraperitoneally administered with chlorpheniramine at 10 mg·kg-1·d-1 for 14 consecutive days,with 5 mg/kg of LPS or an equal volume of normal saline administered on day 7.The LPS group and Control group were intraperitoneally administered with equal volumes of the solvent for 14 days,with 5 mg/kg of LPS or normal saline administered on day 7.Behavioral changes were assessed using the open field test,novel object recognition test,and Y-maze test.Western blot was used to detect the levels of hippocampal interleukin-6(IL-6),interleukin-1β(IL-1β),and myelin basic protein(MBP).Immunofluorescence was used to observe hippocampal microglial cell counts,as well as the expression of MBP,and c-fos,a marker of activity-related neurons.Results Compared with the Control group,the LPS group showed no statistical differences in the total distance traveled or time spent in the center zone of the open field test(P>0.05).However,the LPS group presented decreases in the discrimination index in the novel object recognition test,and the spontaneous alternation rate in the Y-maze test,along with in-creased IL-6 and IL-1βexpression levels,microglial cell counts,as well as reduction in MBP expression and the number of c-fos-positive neurons(P<0.05).Compared with the LPS group,the LPS+CLE group showed no statistical differences in the open field test(P>0.05).However,the LPS+CLE group presented increases in the discrimination index in the novel object recognition test,spontaneous alternation rate in Y-maze test,along with increases in MBP expression and the number of c-fos-positive neurons(P<0.05).Conclusions Chlorpheniramine may improve cognitive dysfunction in the SAE mouse model

关 键 词：脓毒症相关性脑病 海马 髓鞘 氯马斯汀 脂多糖 认知功能损伤 

分 类 号：R741[医药卫生—神经病学与精神病学] R96[医药卫生—临床医学]