机构地区:[1]华北理工大学公共卫生学院,唐山063210 [2]华北理工大学实验动物中心,唐山063210 [3]华北理工大学临床医学院,唐山063210
出 处:《中华行为医学与脑科学杂志》2022年第11期961-967,共7页Chinese Journal of Behavioral Medicine and Brain Science
基 金:国家自然科学基金(82073598)。
摘 要:目的探究纳米氧化铅暴露对小鼠学习记忆和空间探索能力的影响以及脑组织白细胞浸润在纳米氧化铅致神经行为损伤中的作用。方法60只雄性SPF级昆明小鼠按体质量匹配法分为对照组、纳米氧化铅低、中、高剂量组,每组15只。纳米氧化铅低、中、高剂量组小鼠分别腹腔注射5 mg·kg-1、10 mg·kg-1、20 mg·kg-1的纳米氧化铅,对照组小鼠腹腔注射等量0.9%氯化钠溶液,1次/d,持续28 d。Morris水迷宫实验和旷场实验检测小鼠的学习记忆和空间探索能力。Western blot检测小鼠海马组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-1β(interleukin-1β,IL-1β)蛋白表达水平,小鼠脑微血管中细胞间黏附因子-1(intercellular cell adhesion molecule-1,CAM-1)、血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)蛋白表达水平,小鼠血液白细胞中淋巴功能相关抗原-1(lymphocyte function-associated antigen-1,LFA-1)蛋白表达水平。流式细胞术检测小鼠脑组织中白细胞浸润比例。采用SPSS 20.0软件进行统计学分析,Morris水迷宫数据采用重复测量方差分析,其他数据多组间比较采用单因素方差分析,进一步两两比较采用Tukey’s检验;采用Pearson相关分析脑组织白细胞比例、TNF-α、IL-1β与神经行为指标的相关性。结果Morris水迷宫结果显示,四组小鼠的逃避潜伏期存在组别与时间的交互作用(F=3.21,P<0.05)。纳米氧化铅中、高剂量组小鼠的逃避潜伏期均高于对照组(均P<0.05)、穿越平台次数均低于对照组(均P<0.05)。旷场实验结果显示,四组小鼠的中心区域停留时间差异有统计学意义(F=119.10,P<0.01),纳米氧化铅中、高剂量组小鼠站立总次数均低于对照组(均P<0.01)。Western blot结果显示,四组小鼠海马组织TNF-α和IL-1β的蛋白表达均差异有统计学意义(F=7.21,9.89,均P<0.05)。纳米氧化铅高剂量组小鼠海马组织TNF-α[(1.03±0.30),(0.35±0.10)]和IL-Objective To investigate the effect of nano lead oxide(nano-PbO)exposure on learning and memory as well as spatial exploration ability in the mice,and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods A total of 60 male SPF grade Kunming mice were divided into control group,low-dose nano-PbO group,medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method,with 15 mice in each group.Mice in low,medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg-1,10 mg·kg-1,20 mg·kg-1 nano-PbO,respectively.And mice in the control group were intraperitoneally injected with the same volume of 0.9%normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice.Western blot was used to detect the protein expression of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)in hippocampus of mice,intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)in mouse microvessels and lymphocyte function-associated antigen-1(LAF-1)in mouse blood leukocyte.The proportion of leukocytes in mouse brain was detected by flow cytometry.All statistical analyses were performed by SPSS 20.0.Morris water maze data were analyzed by repeated measures ANOVA,the other data among multiple groups were compared by one-way ANOVA,and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells,TNF-αand IL-1βin brain tissue.Results Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time(F=3.21,P<0.05).The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group(both P<0.05),and the numbers of cros
关 键 词:纳米氧化铅 认知功能损伤 白细胞浸润 细胞间黏附因子-1 血管细胞黏附分子-1 小鼠
分 类 号:R114[医药卫生—卫生毒理学]
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