铅暴露和高脂饮食对小鼠中枢神经系统炎症及Th1/Th2细胞比例变化的影响研究  

Effects of lead exposure and high-fat diet on central nervous system inflammation and changes in Th1/Th2 cell ratio in mice

作　　者：吴磊 王艳 何滨 王俊峰 王唯成 李爽 张艳淑 WU Lei;WANG Yan;HE Bin;WANG Jun-feng;WANG Wei-cheng;LI Shuang;ZHANG Yan-shu(School of Public Health,North China University of Science and Technology,Tangshan Hebei 063210,China;Affiliated Hospital of North China University of Science and Technology,Tangshan Hebei 063000,China;Laboratory Animal Center,North China University of Science and Technology,Tangshan Hebei 063210,China)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063210 [2]华北理工大学附属医院,河北唐山063000 [3]华北理工大学实验动物中心,河北唐山063210

出　　处：《毒理学杂志》2020年第4期275-280,共6页Journal of Toxicology

基　　金：国家自然科学基金(81673208);河北省博士研究生创新资助项目(CXZZBS2018140);河北省高等学校科学研究计划(QN2018086);唐山市科学技术研究与发展计划(19130214g)。

摘　　要：目的探讨Th1和Th2细胞在铅暴露和高脂饮食作用下中枢神经系统损伤中的作用,以期为铅暴露和高脂饮食致神经损伤的生物标志研究提供新的靶点。方法SPF级雄性C57BL/6J小鼠60只,随机分为对照组、高脂饮食组、铅暴露组和高脂饮食+铅暴露组。采用质量浓度为300 mg/L的醋酸铅饮用水进行染毒,染毒时间为16周。应用Morris水迷宫实验对小鼠进行神经行为测试,采用电感耦合等离子体-质谱仪检测海马组织中铅水平,应用ELISA法和试剂盒检测小鼠血清中总胆固醇(T-CHO)、甘油三酯(TG)、海马中IFN-γ、IL-4、IL-1β、IL-6、IL-10和TNF-α含量的变化,应用流式细胞术检测脑组织中Th1(CD4+IFN-γ+)和Th2(CD4+IL-4+)细胞比例。结果Morris水迷宫试验结果显示,高脂饮食组和铅暴露组小鼠的潜伏期高于对照组,穿台次数下降,差异有统计学意义(P<0.05)。与高脂饮食组及铅暴露组相比,高脂饮食+铅暴露组第3天潜伏期明显延长,穿台次数减少,差异有统计学意义(P<0.05)。此外,分别与对照组和高脂饮食组比较,铅暴露组和高脂饮食+铅暴露组小鼠海马组织中铅水平均升高,差异有统计学意义(P<0.05)。海马中炎症因子的改变:高脂饮食组、铅暴露组小鼠IL-1β、IL-6、IL-10和TNF-α含量较对照组升高,且高脂饮食+铅暴露组小鼠IL-1β、TNF-α含量明显高于高脂饮食组或铅暴露组。与对照组相比,高脂饮食组和铅暴露组小鼠脑组织中CD4+IFN-γ+(Th1)细胞比例上升,CD4+IL-4+(Th2)细胞比例降低;且高脂饮食+铅暴露组脑组织CD4+IFN-γ+(Th1)细胞比例明显高于高脂饮食组或铅暴露组,CD4+IL-4+(Th2)细胞比例明显降低(P<0.05);其释放的炎症因子IFN-γ和IL-4的变化趋势与细胞比例相似。结论高脂饮食铅暴露后可加剧小鼠神经炎症,Th1/Th2细胞比例失衡可能参与了高脂饮食铅暴露小鼠中枢神经系统损伤的过程。Objective To investigate the role of Th1 and Th2 cells in central nervous system injury induced by lead exposure and high-fat diet,in order to provide new targets for the screening biomarkers of neural damage caused by lead exposure and high-fat diet.Methods Sixty SPF-grade male C57BL/6J mice were randomly divided into control group,high-fat diet group,lead exposure group,high fat diet and lead exposure group.Drinking water with a concentration of 300 mg/L lead acetate was used for exposure(lasting 16 weeks).The Morris water maze experiment was used to test the neural behavior of mice.The lead level in hippocampus was detected by inductively coupled plasma-mass spectrometry.The total cholesterol(T-CHO)and triglyceride(TG)in serum and the changes of IFN-γ,IL-4,IL-1β,IL-6,IL-10,TNF-αin hippocampus were measured by ELISA and kits,Th1(CD4+IFN-γ+)and Th2(CD4+IL-4+)cell ratio in brain tissue was detected by flow cytometry.Results The latencys of mice in the high-fat diet group and the lead exposed group were higher than that in the control group,and the number of penetrating sessions decreased(P<0.05).Compared with the high-fat diet group and the lead-exposed group,the latencys of the high fat diet and lead exposure group were significantly longer on the third day,and the number of penetrating sessions decreased(P<0.05).In addition,compared with the control group and the high-fat diet group,the lead levels in the hippocampus of mice in the lead exposure group and the high fat diet and lead exposure group were increased(P<0.05).The levels of IL-1β,IL-6,IL-10,TNF-αin mice of high-fat diet group,lead exposure group were higher than those in the control group.The contents of IL-1βand TNF-αin the high fat diet and lead exposure group were significantly higher than those in the high-fat diet group or the lead exposure group.Compared with the control group,the proportion of CD4+IFN-γ+(Th1)cells in the brain tissue of the high-fat diet and leadexposed mice increased,and the proportion of CD4+IL-4+(Th2)cells decreased.

关 键 词：铅 高脂饮食 TH1细胞 TH2细胞 

分 类 号：R135[医药卫生—劳动卫生]