NF-κB信号通路在急性弓形虫感染小鼠神经系统功能异常中的调控作用  

The regulatory effect of NF-κB signaling on nervous system dysfunction in mice infected with Toxoplasma gondii

作　　者：陈莹莹[1] 管益涛[1] 刘海涛 聂清[1] 田蒙蒙 CHEN Ying-ying;GUAN Yi-tao;LIU Hai-tao;NIE Qing;TIAN Meng-meng(Wei fang Center for Disease Control and Prevention,Weifang 261061,Shandong,China;Army Hospital of the 80th army group,We-ifiing 261100,Shandong,China)

机构地区：[1]潍坊市疾病预防控制中心,山东潍坊201061 [2]陆军第八十集团军医院

出　　处：《中国病原生物学杂志》2021年第6期686-690,共5页Journal of Pathogen Biology

基　　金：2019年度潍坊市卫生健康委科研计划项目(No.wfwsjk2019046)。

摘　　要：目的探究NF-κB信号通路的活化对弓形虫感染过程中神经系统功能异常的调控作用。方法将C57BL/6小鼠随机分为感染组(TDI)和对照组(NC),使用浓度为2×104个/ml的RH株弓形虫速殖子腹腔感染TDI组小鼠,NC组注射等量生理盐水。通过水迷宫实验(包含定航实验和空间探索实验,使用SuperMaze水迷宫图像记录系统进行监测、分析)、细胞因子检测(ELISA法,应用SoftMax Pro 4.3.1LS软件计算细胞因子含量)、Western blot(使用BCA法进行定量)分别检测TDI组和NC组小鼠学习记忆及认知能力、血清中IL-6和TNF-α产生水平、脑组织中NF-κB和caspase3蛋白水平,采用SPSS 17.0统计软件进行数据分析。结果与NC组相比,感染第3、4、5 d TDI组小鼠逃避潜伏期延长、目标象限花费时间明显减少、新物体认知能力显著降低(均P<0.01);TDI组小鼠脑组织中NF-κB蛋白为(1.10±0.01)pg/ml,是NC组(0.51±0.01)pg/ml的2.16倍(P<0.01);TDI组小鼠外周血中TNF-α、IL-6的水平显著升高,分别是NC组的10倍、15倍(均P<0.01);TDI组小鼠脑组织中caspase3蛋白显著升高,为(0.44±0.05)pg/ml,是NC组(0.31±0.02)pg/ml的1.42倍(P<0.01)。结论急性弓形虫感染过程中,小鼠的学习记忆和认知能力受到影响,可能与NF-κB信号通路的活化密切相关。其作用的潜在机制可能是NF-κB活化后诱导TNF-α及IL-6炎性细胞因子分泌增加和/或诱导caspase 3凋亡蛋白的表达从而引起脑神经胶质细胞凋亡而发挥作用。Objective To investigate the regulatory function of activation of the NF-κB signaling pathway in nervous system dysfunction in mice infected with Toxoplasma gondii.Methods Mice were randomly divided into an infection group(TDI)and a control group(NC).The concentration of the RH strain of T.gondii was adjusted to 2×104/mL,and the TDI group was intraperitoneally infected with T.gondii while the NC group was injected with the same volume of saline.The Morris water maze test(including the hidden platform test and probe trial test,with the SuperMaze video system for monitoring and analysis),cytokine measurement(using ELISA and the software SoftMax Pro 4.3.1 LS to calculate the levels of cytokines)and Western blotting(quantified using a BCA assay)were used to analyze the learning and memory ability,the levels of IL-6 and TNF-αproduction,and the expression of NF-κB and Caspase-3 protein in brain tissue from mice in the TDI and NC groups.SPSS 17.0 was then used to analyze the data.Results Compared to the NC group,the TDI group had a markedly longer escape latency,it spent significantly less time in the target zone,and it had significantly less ability to recognize new objects on days 3,4,and 5.The level of NF-κB protein in the brains of the TDI group(1.10±0.01 pg/ml)was significantly higher than that in the NC group(0.51±0.01 pg/ml);the level of NF-κB protein in the TDI group was 2.16 times that in the NC group(P<0.01).The levels of TNF-αand IL-6 increased significantly in the TDI group compared to levels in the NC group,and the levels were 10 times and 15 times those in the NC group(P<0.01).In addition,the level of caspase-3 protein in the brains of mice in the TDI group(0.44±0.05 pg/ml)was significantly higher than that in the NC group(0.31±0.02)pg/ml;the level of caspase-3 protein in the TDI group was 1.42 times that in the NC group(P<0.01).Conclusion Learning,memory,and perception were affected in mice infected with T.gondii.That impairment may be correlated with activation of the NF-κB signaling pathway.

关 键 词：弓形虫 NF-ΚB信号通路 脑神经系统功能 

分 类 号：R382.5[医药卫生—医学寄生虫学]