TREM2过表达减轻大鼠颅脑创伤后的认知缺陷  

Over-expression of TREM2 alleviates cognitive impairment after traumatic brain injury in rats

作　　者：杨齐 许峰 焦阳 张赛 孙中磊 YANG Qi;XU Feng;JIAO Yang;ZHANG Sai;SUN Zhong-lei(Department of Neurosurgery, Zaozhuang Mining Group Central Hospital, Zaozhuang 277000;Tianjin Key Laboratory of Neuro Trauma Repair, Armed Police Characteristic Medical Center, Tianjin 300162, China)

机构地区：[1]枣庄矿业集团中心医院神经外科,山东枣庄277000 [2]武警特色医学中心,天津市神经创伤修复重点实验室,天津300162

出　　处：《基础医学与临床》2021年第12期1724-1729,共6页Basic and Clinical Medicine

基　　金：国家重点研究发展计划(2016YFC1101503)。

摘　　要：目的研究髓细胞触发受体2(TREM2)过表达对大鼠颅脑创伤(TBI)认知缺陷的影响及其可能机制。方法将大鼠随机分为对照组和TBI(皮质撞击致伤法)后2、5、7、14和28 d组,每组n=8。用RT-qPCR和Western blot检测脑组织TREM2 mRNA及蛋白水平;将余32只大鼠随机分为4组:对照组、TBI组、(TBI+Null)组和(TBI+TREM2)组,每组n=8,(TBI+Null)组脑室内注射对照慢病毒载体,(TBI+TREM2)组脑室内注射等量编码TREM2的慢病毒载体;Morris水迷宫评估各组大鼠记忆功能;RT-qPCR和Western blot评估各组大鼠脑组织小胶质细胞表型(iNOS和Arg-1)、神经炎性相关因子(IL-1β、IL-6、IL-4和IL-10)和认知相关蛋白[淀粉样蛋白β1-42(Aβ1-42)和tau]表达水平。结果TBI组与对照组相比TREM2、TREM2 mRNA、平均逃避潜伏期、iNOS、IL-1β、IL-6、Aβ1-42和tau表达增加,Arg-1、IL-4和IL-10表达减少(P<0.05);(TBI+TREM2)组能显著缓解TBI造成的平均逃避潜伏期、iNOS、IL-1β、IL-6、Aβ1-42和tau表达增加,以及Arg-1、IL-4和IL-10表达减少(P<0.05)。结论TREM2过表达可调节TBI大鼠脑组织小胶质细胞表型,减少认知相关蛋白(Aβ1-42、tau)表达,改善学习记忆功能。Objective To explore the effect of over-expression of triggering receptor on dementia model after traumatic brain injury(TBI)in rat model and potential mechanism.Methods Rats were randomly divided into control group and TBI test groups of 2,5,7,14 and 28 days(n=8).RT-qPCR and Western blot were used to detect trem2 mRNA and protein levels in brain tissues.The remaining 32 rats were randomly divided into 4 groups(n=8):control group,TBI group,(TBI+Null)group and(TBI+TREM2)group.The(TBI+Null)group was injected with control lentiviral vector,and the(TBI+TREM2)group was injected with the same amount of lentiviral vector encoding TREM2.The memory function of rats in each group was assessed by Morris water maze,and the expression of microglia phenotypes(iNOS and Arg-1),neuroinflammatory related factors(IL-1β,IL-6,IL-4 andIL-10)and cognition-related proteins[amyloidβ1-42(Aβ1-42)and tau]in brain tissues of rats from each group were assessed by RT-qPCR and Western blot.Results Compared with the control group,the expressions of TREM2,TREM2 mRNA,mean escape latency,iNOS,IL-1β,IL-6,Aβ1-42 and Tau were all increased in TBI group,while the expression of Arg-1,IL-4 and IL-10 significantly decreased(P<0.05).(TBI+TREM2)group significantly alleviated the mean escape latency,increased expression of iNOS,IL-1β,IL-6,Aβ1-42 and Tau,and decreased expression of Arg-1,IL-4 and IL-10(P<0.05).Conclusions TREM2 over-expression can regulate the microglial phenotype in brain tissue of TBI rats,reduce the expression of cognition-related proteins(Aβ1-42,tau),and improve the learning and memory function of the animal model.

关 键 词：颅脑创伤 髓细胞触发受体2 认知障碍 淀粉样蛋白β1-42 

分 类 号：R651.1[医药卫生—外科学]