乙酸铅与邻苯二甲酸双(2-乙基己基)酯联合染毒对小鼠学习记忆能力的影响
Effects of Lead Acetate Combined with Diethylhexyl Phthalate on Learning and Memory Ability in Mice
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摘要: 塑料包装制品中，邻苯二甲酸双（2-乙基己基）酯（DEHP）为重要的增塑剂，铅盐为必不可少的热稳定剂，二者单体毒性均得到证实。为探究两者的联合作用，采用效应相加模型对联合毒性方式进行评价。选择适龄昆明种小鼠染毒，DEHP染毒浓度为10、50和200 mg·kg-1，以0.1 mL·（10 g）-1的剂量灌胃染毒，铅组用1 g·L-1乙酸铅通过自由饮水进行染毒，连续染毒6周，染毒后观察其行为学改变，测定其脑组织氧化损伤指标和神经递质类指标。结果表明，各组小鼠的肺脏、脾脏、心脏和肾脏系数，无明显差异；随着DEHP浓度增加，脑组织重量逐渐降低，肝脏重量在中剂量DEHP组降低，在高剂量组有所增加，表明DEHP对脑部发育有影响，且对肝脏具有毒性作用，并可能在肝脏产生富集作用。小鼠Morris水迷宫、跳台实验和避暗实验结果表明，随DEHP浓度增加，小鼠空间学习能力受到的损害更加严重，可导致空间记忆能力障碍。小鼠脑组织各生物学指标测定结果显示，随着DEHP浓度增加，脑组织中丙二醛（MDA）含量、一氧化氮（NO）含量、单胺氧化酶（MAO）和乙酰胆碱酯酶（AchE）活性逐渐增加，联合染毒组与铅组和对应剂量DEHP染毒组相比，上述4个指标值显著增加；随着DEHP浓度增加，脑组织中过氧化氢酶（CAT）活性、还原型谷胱甘肽（GSH）含量和总抗氧化能力逐渐降低，联合染毒组与铅组和对应剂量DEHP染毒组相比，上述二者明显降低。对铅和DEHP的联合毒性作用方式进行评价，表现为协同作用。Abstract: In plastic packaging products, diethylhexyl phthalate (DEHP) is an important plasticizer and lead salt is an essential thermal stabilizer. In order to explore the combined effects of DEHP and Pb, Kunming mice were selected to be treated with DEHP at a concentration of 10, 50 and 200 mg·kg-1, with 0.1 mL·(10 g)-1 dose by gavage. The lead group was treated with 1 g·L-1 lead acetate through free drinking water. The exposure last for 6 weeks. The results showed that there was no significant difference in the organ coefficients including lung, spleen, heart and kidney in each treatment group by comparing with the control. With the increase of DEHP concentration, the weight of brain tissue gradually decreased, while the weight of liver decreased at medium dose and became heavier at high dose. It is indicated that DEHP has an impact on brain development, and DEHP has a toxic effect on liver with an accumulation effect as well. The results of Morris water maze, platform jumping experiment and dark avoidance experiment showed that the spatial learning ability of mice was seriously impaired with the increase of DEHP concentration. The results showed that the contents of malondialdehyde (MDA) and nitric oxide (NO), and the activities of monoamine oxidase (MAO) and acetylcholinesterase (AchE) were increased gradually with the increase of DEHP concentration, and the combined exposure group increased more significantly compared with lead group and corresponding dose of DEHP exposure group. With the increase of DEHP concentration, catalase (CAT) activity, glutathione (GSH) content and total antioxidant capacity in brain tissues gradually decreased and the combined exposure group decreased more significantly compared with lead group and corresponding dose of DEHP exposure group. The effect of lead and DEHP was evaluated to be synergistic.
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Key words:
- lead /
- DEHP /
- combined effect /
- learning and memory ability
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