TREM2过表达减轻大鼠颅脑创伤后的认知缺陷

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (12): 1724-1729.

TREM2过表达减轻大鼠颅脑创伤后的认知缺陷

杨齐¹, 许峰¹, 焦阳¹, 张赛², 孙中磊^1,2*

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

收稿日期:2020-12-31 修回日期:2021-04-30 发布日期:2021-12-03
通讯作者: *jzsunzhonglei@163.com
基金资助:
国家重点研究发展计划(2016YFC1101503)

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

YANG Qi¹, XU Feng¹, JIAO Yang¹, ZHANG Sai², SUN Zhong-lei^1,2*

1. Department of Neurosurgery, Zaozhuang Mining Group Central Hospital, Zaozhuang 277000;
2. Tianjin Key Laboratory of Neuro Trauma Repair, Armed Police Characteristic Medical Center, Tianjin 300162, China

Received:2020-12-31 Revised:2021-04-30 Published:2021-12-03
Contact: *jzsunzhonglei@163.com

摘要/Abstract

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。

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

Abstract: 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 and IL-10) and cognition-related proteins [amyloid β1-42 (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.

Key words: traumatic brain injury, triggering receptor expressed on myeloid cells 2(TREM2), cognitive impairment, awyloid β1-42

中图分类号:

R651.1

杨齐, 许峰, 焦阳, 张赛, 孙中磊. TREM2过表达减轻大鼠颅脑创伤后的认知缺陷[J]. 基础医学与临床, 2021, 41(12): 1724-1729.

YANG Qi, XU Feng, JIAO Yang, ZHANG Sai, SUN Zhong-lei. Over-expression of TREM2 alleviates cognitive impairment after traumatic brain injury in rats[J]. Basic & Clinical Medicine, 2021, 41(12): 1724-1729.

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