海马中M-CSF介导小胶质细胞活化参与创伤性脑损伤后认知功能障碍的研究  

Effect of M-CSF mediated activation of hippocampal microglia on cognitive dysfunction after traumatic brain injury

作　　者：向宇豪 王婷婷 顾馨洋 孙华伟 张咏梅 XAING Yuhao;WANG Tingting;GU Xinyang;SUN Huawei;ZAHNG Yongmei(School of Anesthesiology,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China)

机构地区：[1]徐州医科大学麻醉学院,江苏徐州221004

出　　处：《徐州医科大学学报》2023年第10期726-731,共6页Journal of Xuzhou Medical University

基　　金：国家自然科学基金(82071228);大学生科研与实践创新计划项目(202110313013Z)。

摘　　要：目的探究巨噬细胞集落刺激因子(M-CSF)在创伤性脑损伤后认知功能障碍中的作用机制。方法将成年雄性SD大鼠随机分为3组:正常对照组(control组)、假手术组(sham组)、创伤性脑损伤组(TBI组)。依据Feeney自由落体模型制备创伤性脑损伤模型,造模成功后使其自由活动与进食。采用Morris水迷宫定位航行实验、平衡木行走实验检测创伤性脑损伤后第1、3、5、7天大鼠的认知和平衡能力。采用Western blot法检测创伤性脑损伤后各时间点海马中CA1区域内M-CSF及小胶质细胞标志物IBA1蛋白的表达水平。采用免疫荧光染色观察创伤性脑损伤后第3天海马CA1区域M-CSF和IBA1的表达。采用Sholl分析,观察小胶质细胞在创伤性脑损伤后第3天的形态改变。结果与sham组相比,TBI组在损伤后第1、3、5天逃避潜伏期显著延长,平衡木行走实验评分明显升高(P<0.05)。Western blot显示创伤性脑损伤后第3天海马CA1中M-CSF及小胶质细胞标记物IBA1表达水平较sham组显著增高(P<0.05)。免疫荧光染色显示,创伤性脑损伤后第3天海马CA1中M-CSF和IBA1的表达较sham组显著升高(P<0.05)。Sholl分析显示小胶质细胞明显活化。结论创伤性脑损伤后大鼠的认知功能障碍与平衡能力损伤与M-CSF介导的小胶质细胞活化产生的炎症反应相关,并于损伤后第3天达到高峰。Objective To investigate the role of macrophage colony-stimulating factor(M-CSF)in cognitive dysfunction after traumatic brain injury(TBI).Methods Adult male SD rats were randomly divided into three groups:a normal control(control)group,a sham operation(sham)group,and a TBI group.A traumatic brain injury model was established according to the Feeney Free fall model.After successful modeling,the animals were allowed to free access to food and movement.Their cognitive function and balance abilities were evaluated by place navigation test and balance beam walking test on days 1,3,5 and 7 after TBI.The expression of M-CSF and microglia marker IBA1 in hippocampal CA1 region at each time point after TBI was detected by Western blot.The expression of M-CSF and IBA1 in hippocampal CA1 region on day 3 after TBI was observed by immunofluorescence staining.The morphological changes of microglia on day 3 after TBI were measured by Sholl analysis.Results Compared with the sham group,the TBI group showed remarkably extended escaping latency and increased beam walking test scores on days 1,3 and 5 after TBI(P<0.05).According to Western blot analysis,the levels of M-CSF and IBA1 in the hippocampal CA1 region significantly increased on day 3 after TBI,compared with those in the sham group.Furthermore,immunofluorescence staining showed that the levels of M-CSF and IBA1 in the hippocampal CA1 region on day 3 after TBI significantly increased,compared with those in the sham group.Sholl analysis indicated significant activation of microglia.Conclusions Cognitive dysfunction and damage of balance ability in rats after TBI are associated with an inflammatory response generated by M-CSF-mediated microglia activation,which peaks on day 3 after TBI.

关 键 词：创伤性脑损伤 海马 巨噬细胞集落刺激因子 小胶质细胞 认知功能障碍 

分 类 号：R651.15[医药卫生—外科学]