氯化镉对小鼠脑组织氧化损伤及核因子κB表达的影响  

Effect of cadmium choride on oxidative damage and expression of NF-κB in brain tissue of mice

作　　者：张玉媛[1] 陈雪[1] 王允[1] 王春华[1] 

机构地区：[1]蚌埠医学院预防医学系,蚌埠233030

出　　处：《卫生研究》2017年第5期807-812,共6页Journal of Hygiene Research

基　　金：安徽省高校自然科学研究项目(No.KJ2015A212;KJ2016A476);安徽省高等学校省级质量工程特色专业建设项目(No.2014tszy019)

摘　　要：目的探讨氯化镉(CdCl_2)对小鼠脑组织氧化损伤以及核因子κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、可溶性小鼠细胞间粘附分子(ICAM-1)表达的影响。方法 32只健康成年ICR雄鼠随机分为CdCl_2 2.0、1.0和0.5 mg/kg处理组及生理盐水(NS)对照组,各组经腹腔注射CdCl_2,连续14 d。末次染毒后进行旷场实验;颈椎脱臼处死取脑组织,测定活性氧(ROS)含量,ELISA法检测TNF-α和ICAM-1的表达,免疫组化及蛋白质印迹法观察脑组织NF-κB P65蛋白的表达,HE染色大脑神经病理学检查。结果随CdCl_2剂量的增加,实验动物体重增长程度下降(P<0.05),CdCl_2 2.0 mg/kg组体重增加程度显著低于其他各组(P<0.05)。在旷场实验中,CdCl_2 2.0 mg/kg组跨越格子数显著高于NS对照组(P<0.05)。CdCl_2 2.0和1.0mg/kg组小鼠脑组织中ROS水平增高(P<0.05)、CdCl_2 2.0 mg/kg组TNF-α表达增加(P<0.05),ICAM-1各组间差异无统计学意义。免疫组化结果和Western blot均提示,CdCl_2 2.0 mg/kg组NF-κB P65表达增加。病理检查发现,CdCl_2 2.0 mg/kg组大脑皮质及海马层细胞稀疏。结论镉暴露后小鼠脑组织中ROS表达增加,ROS可以激活NF-κB通路,上调炎性细胞因子TNF-α的表达。Objective To investigate the oxidative damage induced by cadmium choride and the expression of nuclear factor κB（ NF-κB）,tumor necrosis factor-α（ TNF-α） and intercellular cell adhesion molecule-1（ ICAM-1） in brain tissue of mice. Methods A total of 32 adult ICR mice were divided into 4 groups randomly including CdCl_2 2. 0,1. 0 and 0. 5 mg/kg and NS control group,all mice were through intraperitoneally injected administration for 14 days,after the last exposure,open-field test were used and all mice were sacrificed by cervical dislocation,the expression of reactive oxygen species（ ROS）was measured and the expression of TNF-α,ICAM-1 were observed by ELISA,the level of NF-κB P65 in the brain were detected by immunohistochemistry and western blot,the slices of the brain were stained with HE for histopathological examination. Results Thebody weight gain in CdCl_22. 0 mg/kg was significant lower than others（ P 0. 05）,the number of crossing lattice in CdCl_2 2. 0 mg/kg was higher than the NS control group in the open field test. The expression of ROS increased in CdCl_2 2. 0 and 1. 0 mg/kg groups（ P 0. 05）,the expression of TNF-α increased in CdCl_2 2. 0 mg/kg group（ P 0. 05）,no obvious change was found among every group of ICAM-1,the expression of NF-κB P65 in the brain increased in cadmium 2. 0 mg/kg group. The neuropathological test showed that the cerebral cortex and hippocampal cells were more loose in 2. 0 mg/kg group than the control. Conclusion The level of ROS in mouse brain tissue increased,NF-κB pathway was activated by ROS and the expression of inflammatory cytokine TNF-α was increased.

关 键 词：氯化镉 小鼠 活性氧 核因子ΚB 肿瘤坏死因子-Α 细胞间粘附分子 

分 类 号：R994.6[医药卫生—毒理学] Q593.2[医药卫生—药学]