小胶质细胞介导的TRPV1在小鼠缺血性脑卒中后抑郁样行为中的作用和机制  

Role and mechanism of microglia-mediated TRPV1 in depression-like behavior after ischemic stroke in mice

作　　者：刘丹 方天赐 李明玥 宋远见 王玉兰 LIU Dan;FANG Tianci;LI Mingyue;SONG Yuanjian;WANG Yulan(Department of Human Anatomy,Xuzhou Medical University,Xuzhou 221000,China)

机构地区：[1]徐州医科大学人体解剖学教研室,徐州221000 [2]徐州医科大学临床医学系,徐州221000 [3]徐州医科大学遗传学教研室,徐州市医学遗传与转化工程中心,徐州221000 [4]徐州医科大学基础医学国家级实验教学中心,徐州221000

出　　处：《中国免疫学杂志》2022年第5期541-544,共4页Chinese Journal of Immunology

基　　金：江苏省“六大人才高峰”高层次人才培养对象项目(WSN-089);徐州医科大学2019年大学生创新实践训练计划项目(201910313108H)。

摘　　要：目的:探讨TRPV1对缺血性脑卒中后抑郁样行为的作用和机制。方法:45只雄性小鼠随机分为3组:假手术组(sham),脑缺血再灌注组(I/R),脑缺血再灌注+TRPV1抑制剂Capsazepine组(I/R+CPZ)。建立小鼠大脑中动脉阻塞模型(MCAO),HE染色观察病理性损伤;免疫荧光染色观察小胶质细胞的激活;免疫印迹检测IL-1β的表达;7 d后进行强迫游泳和悬尾实验。结果:行为学检测显示与I/R组相比,TRPV1抑制剂可显著改善小鼠的抑郁样行为(P<0.001)。HE染色结果表明,I/R+CPZ组杏仁核区病理损伤明显减轻。免疫荧光染色观察结果显示,杏仁核小胶质细胞有TRPV1的表达,且I/R+CPZ组与I/R组相比,小胶质细胞的激活明显减少(P<0.001)。免疫印迹检测结果显示,给药后IL-1β的表达量明显少于IR组(P<0.05)。结论:抑制TRPV1可减轻炎症反应,改善缺血性脑卒中后小鼠的抑郁样行为。Objective:To explore the effect and mechanism of TRPV1 on depression-like behavior after ischemic stroke.Methods:Forty-five male mice were randomly divided into 3 groups:sham group(sham),ischemia/reperfusion group(I/R),ischemia/reperfusion+Capsazepine group(I/R+CPZ).The middle cerebral artery occlusion model(MCAO)was established.HE staining was used to observe the pathological damage;immunofluorescence staining was used to observe the activation of microglia,and Western blot was used to detect IL-1βexpression.Forced swim test and tail suspension test were performed 7 d later.Results:Compared with I/R group,behavioral tests showed that TRPV1 significantly improved the depressive-like behavior(P<0.001).HE staining showed that the pathological damage of amygdala in I/R+CPZ group was significantly reduced.Immunofluorescence staining showed that TRPV1 was expressed in amygdala microglia and the activation of microglia was significantly reduced in I/R+CPZ group compared with the I/R group(P<0.001).Western blot detection showed that expression of IL-1βafter administration was significantly lower than that in IR group(P<0.05).Conclusion:Inhibition of TRPV1 can reduce inflammation and improve depression-like behavior in mice after ischemic stroke.

关 键 词：缺血性脑卒中 卒中后抑郁 辣椒素受体1 CAPSAZEPINE 炎症 

分 类 号：R743.3[医药卫生—神经病学与精神病学]