氯马斯汀对慢性疼痛模型小鼠抑郁样行为改善作用及神经机制研究  

Improvement and neural mechanism of clemastine on depressive-like behavior in chronic pain model mice

作　　者：梁玥 黄艳梅 刘雪琴 曹文宇[3] 陈玲 钟小林 Liang Yue;Huang Yanmei;Liu Xueqin;Cao Wenyu;Chen Ling;Zhong Xiaolin(Department of Laboratory Medicine,the First Affiliated Hospital of University of South China,Hengyang 421001,China;Department of Endocrinology and Metabolism,the First Affiliated Hospital of University of South China,Hengyang 421001,China;Clinical Anatomy and Reproductive Medicine Application Institute,University of South China,Hengyang 421001,China)

机构地区：[1]南华大学附属第一医院临床医学检验科,衡阳421001 [2]南华大学附属第一医院内分泌与代谢疾病研究所,衡阳421001 [3]南华大学应用解剖与生殖医学研究所,衡阳421001

出　　处：《中华行为医学与脑科学杂志》2024年第4期289-294,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：湖南省自然科学基金(2023JJ30553)。

摘　　要：目的:探讨氯马斯汀(clemastine,CLE)对完全弗氏佐剂(complete Freund's adjuvant,CFA)诱导的慢性疼痛模型小鼠抑郁样行为的影响和可能的机制。方法:30只雄性C57BL/6J小鼠按照随机数字表法分为生理盐水对照组(NS组)、疼痛模型组(CFA组)、疼痛模型+CLE干预组(CFA-CLE组),每组10只。CFA组、CFA-CLE组小鼠在右后足足底中部皮下注射10μL CFA建立慢性炎性疼痛模型,CFA-CLE组小鼠在CFA注射第7天腹腔注射CLE(10 mg/kg),1次/d,持续14 d,CFA组和NS组小鼠注射等体积0.9%氯化钠溶液。采用von Frey纤维丝检测3组小鼠机械缩足阈值(paw withdrawal mechanical threshold,PWMT);采用旷场实验检测小鼠的活动度,采用糖水偏爱实验、悬尾实验、强迫游泳实验检测小鼠抑郁样行为;采用免疫组织化学染色方法检测小鼠海马区少突胶质细胞标志物髓鞘碱性蛋白(myelin basic protein,MBP)、新生神经元标志物双皮质素(doublecortin,DCX)和成熟神经元标志物微管相关蛋白2(microtubule-associated protein 2,MAP2)的表达情况。采用GraphPad Prism 8.0软件进行统计分析,3组间比较采用单因素方差分析,PWMT结果采用重复测量方差分析。结果:痛阈检测结果显示,时间和组别对PWMT影响的交互效应是显著的(F=4.390,P<0.001),并且时间主效应(F=13.44,P<0.001)与组别主效应(F=25.38,P<0.001)均有显著性。在1 d、7 d、14 d、21 d,CFA组小鼠的PWMT均低于NS组(均P<0.001);CFA组与CFA-CLE组小鼠在1 d、7 d、14 d、21 d的PWMT均显著低于0 d(均P<0.001);而在不同时间点CFA-CLE组小鼠的PWMT与CFA组相比均差异无统计学意义(均P>0.05)。3组小鼠旷场实验中的运动总距离差异无统计学意义(F=1.15,P>0.05)。3组小鼠的糖水偏爱率、悬尾不动时间和强迫游泳不动时间均差异有统计学意义(F=5.46,13.44,14.29,均P<0.05);CFA组小鼠的糖水偏爱率[(65.78±11.61)%]低于NS组[(80.55±6.41)%],悬尾不动时间和强迫游泳不动时间[(124.60±18.16)s,(Objective To study the effect of clemastine(CLE)on pain-related depressive-like behavior induced by complete Freund's adjuvant(CFA)and its possible regulatory mechanism.Methods Thirty C57BL/6J male mice were randomly divided into normal saline control group(NS group),CFA induced pain model group(CFA group)and CFA+CLE intervention group(CFA-CLE group),with 10 mice in each group.The mice in CFA group and CFA-CLE group were subcutaneously injected with 10μL CFA in the middle of the right hind foot to establish the chronic inflammatory pain model.Then 7 days later,mice in CFA-CLE group were intraperitoneally injected with CLE(10 mg/kg)once a day for 14 days,meanwhile mice in CFA group and NS group were injected with an equal volume of 0.9%sodium chloride solution.The von Frey fiber was used to evaluate the paw withdrawal mechanical threshold(PWMT)of mice in the three groups.Open field test was used to detect the activity of mice.Sucrose preference test,tail suspension test(TST)and forced swimming test(FST)were used to detect the depressive-like behavior of mice.Immunohistochemical staining was used to detect the expression of myelin basic protein(MBP)(a marker for oligodendrocytes),doublecortin(DCX)(a marker for newly formed neurons),and microtubule-associated protein 2(MAP2)(a marker for mature neurons)in the hippocampus of mice.GraphPad Prism 8.0 software was used for statistical analysis.Multiple group comparisons were conducted by one-way ANOVA.The pain threshold data was analyzed by repeated ANOVA.Results The results of pain threshold showed that the interaction effect of time and group on PWMT was significant(F=4.390,P<0.001),and both the time main effect(F=13.44,P<0.001)and group main effect(F=25.38,P<0.001)were significant.At 1 d,7 d,14 d,21 d,the PWMT of mice in CFA group were significantly lower than those of NS mice(all P<0.001).The PWMT of mice in CFA group and CFA-CLE group at 1 d,7 d,14 d and 21 d were significantly lower than those at 0 d(all P<0.001).However,there were no significant differences in P

关 键 词：慢性疼痛 氯马斯汀 少突胶质细胞 髓鞘碱性蛋白 神经元可塑性 抑郁样行为 小鼠 

分 类 号：R965[医药卫生—药理学]