髓细胞触发受体2对大鼠颅脑创伤后认知功能障碍的影响  

Effect of triggering receptor expressed on myeloid cells-2 on cognitive dysfunction in rats after traumatic brain injury

作　　者：赵莉 孙中磊 杨齐 刘英富 张赛 ZHAO Li;SUN Zhonglei;YANG Qi;LIU Yingfu;ZHANG Sai(Characteristic Medical Center of Chinese People′s Armed Police Force,Tianjin,300162;Central Hospital of Zaozhuang Mining Group of Shandong Province,Zaozhuang,Shandong,277000;Tianjin Key Laboratory of Neurotrauma Repair,Tianjin,300162;Institute of Nanoantibody of Cangzhou Medical College,Cangzhou,Hebei,061001)

机构地区：[1]中国人民武装警察部队特色医学中心,天津300162 [2]山东省枣庄矿业集团中心医院,山东枣庄277000 [3]天津市神经创伤修复重点实验室,天津300162 [4]沧州医学高等专科学校纳米抗体研究所,河北沧州061001

出　　处：《实用临床医药杂志》2021年第7期25-29,33,共6页Journal of Clinical Medicine in Practice

基　　金：国家重点研究发展计划项目(2016YFC1101503);河北省重点研发计划项目(19272404D)。

摘　　要：目的探索髓细胞触发受体2(TREM2)对大鼠颅脑创伤(TBI)后认知功能障碍的影响及其可能机制。方法将24只大鼠随机分为sham组(假手术)、TBI组和TBI并TREM2组(TREM2过表达),每组8只。TBI组和TBI并TERM2组采用皮质打击构建大鼠TBI模型,sham组仅开骨窗;TREM2过表达模型采用腺病毒相关病毒(AAVrh.10)AAVrh.10 TREM2脑室注射构建,sham组和TBI组注射等量AAVrh.10衣壳AAVrh.10Null。实验28 d,采用Morris水迷宫实验评估各组大鼠学习记忆功能;采用免疫印迹法(Western blot)评估TREM2和认知相关蛋白表达水平,Western blot和免疫荧光评估自噬蛋白表达水平。结果与sham组相比,TBI组大鼠平均逃避潜伏期延长,认知障碍相关蛋白[淀粉样蛋白β_(1-42)(Aβ_(1-42))、tau]表达增加,TREM2、自噬蛋白LC3-Ⅱ、LC3-Ⅱ/LC3-Ⅰ表达增加,P62表达减少,差异均有统计学意义(P<0.05)。与TBI组相比,TBI并TREM2组大鼠平均逃避潜伏期缩短,认知障碍相关蛋白(Aβ_(1-42)、tau)表达减少,TREM2表达增加,自噬蛋白LC3-Ⅱ表达增加,LC3-Ⅱ/LC3-Ⅰ表达增加,P62表达减少,差异均有统计学意义(P<0.05)。结论TREM2过表达可以改善TBI大鼠认知功能缺陷,其机制可能是通过促进小胶质细胞的自噬作用。Objective To explore the effect of triggering receptor expressed on myeloid cells-2(TREM2)on cognitive dysfunction after traumatic brain injury(TBI)in rats and its possible mechanism.Methods Twenty-four rats were randomly divided into sham group(sham operation),TBI group and TBI complicated with TREM2 group(TREM2 overexpression),with 8 rats in each group.TBI rat model was constructed by cortical strike in TBI group and TBI complicated with TREM2 group,and the sham group only opened the bone window.TREM2 overexpression model was constructed by intraventricular injection of adenovirus-associated virus(AAVRH.10)AAVRH.10 TREM2.The Sham group and the TBI group were injected with the same amount of AAVRH.10 Null capsid.After28 days,Morris water maze was used to evaluate the learning and memory function of rats in each group.Western blot was used to evaluate the expression levels of TREM2 and cognition-related proteins,and Western blot as well as immunofluorescence were used to evaluate the expression levels of autophagy proteins.Results Compared to the sham group,average escape latency of TBI group was prolonged,cognitive impairment related proteins[amyloid beta(1-42)(Aβ_(1-42)),tau]expression,TREM2 expression level,autophagy protein LC3-Ⅱexpression and LC3-Ⅱ/LC3-Ⅰexpressionall increased,P62 expression decreased,the differences of the above indicators were statistically significant(P<0.05).Compared with TBI group,the average escape latency of rats in the TBI complicated with TREM2 group was shortened,cognitive impairment related proteins(Aβ_(1-42),tau)was reduced,TREM2 expression,LC3-Ⅱautophagy protein expression and LC3-Ⅱ/LC3-Ⅰexpression all increased,P62 expression decreased,the differences of the above indicators were statistically significant(P<0.05).Conclusion TREM2 overexpression can improve cognitive dysfunction in TBI rats,possibly by mechanism of promoting microglial autophagy.

关 键 词：颅脑创伤 髓细胞触发受体2 阿尔兹海默症 小胶质细胞 自噬 

分 类 号：R651.1[医药卫生—外科学] R749.1[医药卫生—临床医学]