【作者】 刘晓丽；

【导师】 原福胜；

【作者基本信息】 山西医科大学 ， 劳动卫生与环境卫生学， 2010， 硕士

【摘要】 目的：近年来,随着社会发展和人民生活水平的提高,室内装修已成为新的时尚,由此引起的室内空气污染问题日趋严重。甲醛和苯是室内主要挥发性有机物,不仅污染水平高,而且生物毒性大,可能对暴露人群产生联合毒性效应。目前对甲醛和苯的单独毒性作用研究较多,但对于二者联合神经毒性的效应和机制研究较少。本研究旨在探讨甲醛和苯联合染毒对小鼠神经系统的毒性作用及机制,为综合评价甲醛和苯的安全性提供科学依据,为室内环境污染研究提供理论参考。方法：选择健康清洁级昆明种纯系小鼠60只,体重18～22 g,随机分为10组,每组6只,雌雄各半,分别是对照组(清洁空气)(G0),低(1.0mg／m3)(G1)、中(3.0mg／m3)(G2)、高(5.0mg/m3)(G3)剂量甲醛组,低(500mg/m3)(G4)、中(1500mg/m3)(G5)、高(2500mg/m3)(G6)剂量苯组,低(0.5mg/m3甲醛+250mg/m3苯)(G7)、中(1.5mg/m3甲醛+750mg/m3苯)(G8)、高(2.5mg/m3甲醛+1250mg/m3苯)(G9)剂量联合组。采用50 L染毒柜(顶置风扇)进行静式吸入染毒,每天2h,连续染毒14d。染毒结束后,采用跳台实验和Morris水迷宫实验进行神经行为学测试；测试结束后取出脑组织,测定脑组织的SOD活力、MDA含量及DNA损伤情况。结果：1、甲醛、苯单独及联合染毒可导致小鼠学习记忆能力下降：(1)跳台实验,中、高剂量甲醛组,苯组和联合各剂量组潜伏期短于对照组,犯错误次数多于对照组(P<0.05)；与单独染毒组比较,各剂量联合组潜伏期明显缩短(P<0.05)。(2) Morris水迷宫实验：在定位航行实验中,高剂量甲醛组,中、高剂量苯组和各剂量联合组小鼠逃避潜伏期长于对照组(P<0.05),与甲醛、苯单独组比较,中、高剂量联合组逃避潜伏期明显延长(P<0.05);在空间探索实验中,中、高剂量甲醛组,高剂量苯组及各剂量联合组在目标象限游泳时间所占的百分比小于对照组(P<0.05)；与单独染毒组比较,各剂量联合组在目标象限游泳时间所占的百分比显著减小(P<0.05)。2、甲醛、苯单独及联合染毒可导致小鼠脑组织SOD活力降低、MDA含量升高：甲醛和苯单独染毒中、高剂量组及联合各剂量组的SOD活力低于对照组(P<0.05)；各剂量甲醛组、高剂量苯组和联合各剂量组MDA含量高于对照组(P<0.05)。与甲醛、苯单独组比较,联合各剂量组SOD活力明显下降,MDA含量明显升高(P<0.05)。3、甲醛、苯单独及联合染毒可引起小鼠脑细胞DNA断裂作用和DNA-蛋白质交联作用(DNA-protein cross-Links, DPC):与对照组比较,甲醛和苯单独染毒低、中剂量组脑细胞彗星尾部DNA含量增高,尾距增大,中、高剂量组DPC系数升高(P<0.05),联合染毒各剂量组脑细胞彗星尾部DNA含量增高,尾距增大,DPC系数升高(P<0.05)。与甲醛、苯单独组比较,联合染毒各剂量组彗星尾部DNA含量增高,尾距增大,DPC系数明显升高(P<0.05)。结论：甲醛和苯对小鼠具有神经毒性,能降低小鼠的学习记忆能力,引起脑组织脂质过氧化性损伤和脑细胞DNA损伤,低浓度时引起DNA断裂,较高浓度时可以引起明显的DNA-蛋白质交联作用。二者联合染毒对小鼠神经系统毒性可能具有一定的协同作用。脂质过氧化性损伤及DNA损伤可能是甲醛和苯引起小鼠神经系统损伤的重要机制。更多还原

【Abstract】 Objective:In recent years, with the development of society and the continuous improvement of people’s living standards, indoor decorating becomes the trend of fashion, finally the condition of indoor air pollution becomes increasingly serious. Formaldehyde and benzene released by ornament materials have become the main pollutants of indoor air. Formaldehyde and benzene usually exist together indoors in high concentrations, so they can have combined toxic effect on human body. Now there are lots of reports about neurotoxic effect induced by formaldehyde or benzene, but few about neurotoxicity of joint exposure to the two substances. This study is to explore the neurotoxicity of joint exposure to formaldehyde and benzene in mice, to provide scientific basis for the synthetic evaluation of the security of formaldehyde and benzene, and provide theory references for the researches on indoor pollution.Methods:Sixty KM mice were randomly divided into 10 groups. The formaldehyde treatment groups were exposed at dosage of 1 mg/m3,3 mg/m3,5mg/m3, the benzene treatment groups were exposed at dosage of 500 mg/m3,1500 mg/m3,2500 mg/m3 and the formaldehyde and benzene combined treatment groups were exposed at dosage of 0.5 mg/m3+250 mg/m3,1.5 mg/m3+750 mg/m3,2.5 mg/m3+1250 mg/m3 respectively. The mice were exposed to formaldehyde and benzene by static state inhalation in a chamber for 14 days,2 hours a day. Then their behavior of learning and memory were tested by step-down test and Morris water maze experiment, and oxidative damage were detected in the cerebral tissue. The mice were exposed to formaldehyde and benzene by static state inhalation in a chamber for 14 days,2 hours a day. Then their behavior of learning and memory were tested by Morris water maze experiment. At the end, the activities of SOD、the contents of MDA in brains could be determined and DNA damages in brain cells could be observed.Results:1、Formaldehyde and benzene could degrade the learning and memory abilities of mice. (1)Step-down test showed that, the incubation period reduced and number of mistakes increased in the moderate and high dose of formaldehyde treatment group、the moderate and high dose of benzene treatment groups and all the combined treatment groups(P<0.05); the incubation period significantly reduced in the moderate and high dose of combined treatment groups(P<0.05) compared with single exposure.(2)Morris water maze test in space training and learning indicated that escape latency significantly extended in the high dose of formaldehyde treatment group、the moderate and high dose of benzene treatment groups and all the combined treatment groups(P<0.05).Compared with the single exposure groups, escape latency significantly extended in the moderate and high dose of combined treatment groups(P<0.05).In space exploration experiments, the proportion of time of the target quadrant in the moderate and high dose of formaldehyde treatment group、the high dose of benzene treatment groups and all the combined treatment groups were less than the negative control groups(P<0.05).The proportion of time of the target quadrant in the every dose of combined treatment groups were significantly decreased compared with single exposure (P<0.05).2、The activities of SOD in the moderate and high-dose formaldehyde and benzene treatment groups and all the joint exposure groups were decreased. while the contents of MDA increased in the high dose of benzene treatment groups、all the formaldehyde’s and joint exposure groups. Compared with formaldehyde or benzene exposure groups, the activities of SOD in joint exposure groups were significantly decreased (P<0.05) and contents of MDA were obviously increased (P<0.05).3、Formaldehyde and benzene could cause DNA damage in brain cells of mice:Compared with the negative control groups, the tail DNA% and Tail moment were increased in the low and moderate dose of formaldehyde and benzene treatment group(P<0.05).Meanwhile, the content of DPC was increased in the moderate and high dose of formaldehyde and benzene treatment groups(P<0.05). In all the combined treatment groups, the tail DNA%、Tail moment and the content of DPC were significantly increased compared with the negative control groups and single exposure groups(P<0.05).Conclusion:Formaldehyde and benzene had neurotoxicity in mice, it could degrade the learning and memory abilities of mice, result in lipid peroxide in brains and the DNA damage in brain cells of mice. It showed that DNA strand breakage was caused at low levels while DPC was induced at relatively higher levels. Maybe the joint neurotoxicity effect is synergistic. Lipid peroxide and DNA damage might be the important mechanisms of central nervous system function damage in mice induced by formaldehyde and benzene.更多还原