甲醛和苯单独及联合染毒对小鼠神经系统的毒性作用

Neurotoxicity of Joint Exposure to Formaldehyde and Benzene in Mice

  • 摘要:
    目的 研究甲醛和苯单独及联合染毒对小鼠神经系统的毒性作用,为综合评价甲醛和苯的联合毒性提供科学依据。

    方法 选用健康清洁级昆明种纯系小鼠60只,随机分为10组,每组6只,雌雄各半,分别是阴性对照组(清洁空气) (G0);低(1mg/m3) (G1)、中(3mg/m3) (G2)、高(5mg/m3) (G3)剂量甲醛组;低(500mg/m3) (G4)、中(1500mg/m3) (G5)、高(2500 mg/m3) (G6)剂量苯组;低(0.5 mg/m3甲醛+250 mg/m3苯) (G7)、中(1.5 mg/m3甲醛+750 mg/m3苯) (G8)、高(2.5mg/m3甲醛+1250 mg/m3苯) (G9)剂量联合组。采用静式吸入染毒,每天2 h,连续染毒14 d。染毒结束后,采用Morris水迷宫实验检测小鼠的学习记忆能力,并测定脑组织的氧化损伤水平。

    结果 Morris水迷宫实验结果显示:在定位航行实验中,高剂量甲醛组,中、高剂量苯组和各联合剂量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,与对照组比较,中、高剂量甲醛组和高剂量苯组及各联合剂量组在目标象限游泳时间所占百分比减小(P < 0.05);与甲醛、苯单独染毒组比较,各联合剂量组在目标象限游泳时间所占百分比均明显减小(P < 0.05)。甲醛和苯单独染毒中、高剂量组及各联合剂量组的SOD活力均低于阴性对照组(P < 0.05);各剂量甲醛组、高剂量苯组和各联合剂量组MDA含量均高于其阴性对照组(P < 0.05)。与甲醛、苯单独染毒组比较,各联合剂量组SOD活力明显下降(P < 0.05), MDA含量明显升高(P < 0.05)。

    结论 较高剂量甲醛和苯单独染毒对小鼠神经系统有一定毒性作用,甲醛和苯联合染毒对小鼠神经系统的毒性作用大于甲醛、苯单独染毒时的作用,二者联合毒性可能具有协同作用。

     

    Abstract:
    Objective To study the neurotoxicity of joint exposure to formaldehyde and benzene in mice, so as to provide scientific basis for the synthetic evaluation of the toxicity of formaldehyde and benzene.

    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, 5 mg/m3; the benzene treatment groups were exposed at dosage of 500 mg/m3, 1 500 mg/m3, 2 500 mg/m3; and the combined formaldehyde and benzene 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+1 250 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 Morris water maze experiment and oxidative damage was detected in the cerebral tissue.

    Results 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 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 groups, the high dose of benzene treatment group, 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). 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 group, all the formaldehyde's and joint exposure groups increased. 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).

    Conclusion Formaldehyde and benzene have obvious toxic effects on central nervous system in mice. The neurotoxicity of formaldehyde and benzene combined exposure in mice is more severe than their single exposure, which may be caused by synergistic toxic effect.

     

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