三(1,3-二氯-2-丙基)磷酸酯对大鼠的神经毒性效应  

Tris(1,3-dichloro-2-propyl) Phosphate( TDCPP) Induced Neurotoxic Effects in Rats

作　　者：王思敏 李学彦[2] 周启星[1] 胡献刚[1] 邵晓东[2] 张永国[2] Wang Simin;Li Xueyan;Zhou Qixing;Hu Xiangang;Shao Xiaodong;Zhang Yongguo(Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria / Tianjin Key Laboratory of Environmental Remediation and Pollution Control,College of Environmental Science and Engineering,Nankai University,Tianjin 300350,China;Department of Digestion,The General Hospital,Shenyang Military Region,Shenyang 110016,China)

机构地区：[1]南开大学环境科学与工程学院,环境污染过程与基准教育部重点实验室/天津市城市生态环境修复与污染防治重点实验室,天津300350 [2]沈阳军区总医院消化科,沈阳110016

出　　处：《生态毒理学报》2019年第3期186-195,共10页Asian Journal of Ecotoxicology

基　　金：国家自然科学基金面上项目(31670508)

摘　　要：考察三(1,3-二氯-2-丙基)磷酸酯(TDCPP)对大鼠神经系统的毒性效应及其毒性机制,为有机磷阻燃剂(OPFRs)对哺乳动物神经毒性及其临床防治提供基础数据和科学依据。以Sprague-Dawley(SD)大鼠为受试生物,将TDCPP溶于橄榄油配制不同染毒剂量(125、250和500mg·kg^-1·d^-1)进行灌胃处理,溶剂对照组以相同体积的橄榄油进行灌胃,空白对照组不做任何处理,染毒周期为12周。结果表明,溶剂对照组和空白对照组的各项检测指标均无显著性差别(P>0.05)。TDCPP染毒组与对照组之间的差异主要表现为(1)体重变化:染毒期间,TDCPP处理组大鼠的体重与对照组相比有下降的趋势,在第12周中剂量染毒组和高剂量染毒组大鼠体重均显著性低于对照组(P<0.05);(2)行为学实验:Morris水迷宫实验结果表明,高剂量的TDCPP对大鼠的空间学习记忆能力造成影响,主要表现为在定位航行实验中,高剂量染毒组大鼠的逃避潜伏期显著性高于对照组和低剂量染毒组(P<0.05),而在空间探索实验中,高剂量染毒组大鼠在目标象限停留时间显著性低于对照组(P<0.05);(3)生化指标检测:各组间纹状体内多巴胺(DA)含量并无显著性差异(P>0.05),染毒组乙酰胆碱酯酶(AChE)活性与对照组相比显著性降低(P<0.01)且具有剂量依赖性,高剂量染毒组超氧化物歧化酶(SOD)活性显著性降低,高剂量和中剂量染毒组谷胱甘肽(GSH)含量显著性降低(P<0.05),这表明TDCPP对大鼠脑组织造成了氧化损伤,TDCPP染毒组脑组织的炎症因子(TNF-α)水平均高于对照组,且中剂量与高剂量染毒组TNF-α含量显著性高于对照组(P<0.05),揭示TDCPP能引起大鼠脑部的炎症反应,对脑组织造成损伤;(4)纹状体超微结构:电镜结果表明,TDCPP可导致纹状体细胞受到损伤,主要表现为细胞核固缩、线粒体损伤和突触间隙减小。研究表明,TDCPP可引起大鼠体重明显下降,导致大鼠神经细胞损伤,行为改变,This paper aims to investigate the neurotoxicity of tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and the mechanism.Rats were used as the animal model;TDCPP was dissolved in olive oil for preparation of different TDCPP doses (125,250 and 500 mg·kg^-1·d^-1 );the solvent control group was given with the same volume of olive oil.After rats were exposed to TDCPP for 12 weeks,the results showed that there was no difference between solvent control group and blank control group in all indexes.The comparison between TDCPP treatment groups and control group were as follows:(1) During TDCPP treatment for 12 weeks,the rat body weight in TDCPP-exposed groups showed decreasing tendency compared with blank control and solvent control group.At the end of 12th week,the body weight of medium dose group and high dose group were statistically decreased compared with control group (P <0.05).(2) The result of Morris water maze showed that TDCPP can influence the spatial learning and memory ability of rats in high dose group.In positioning navigation experiment,the escape latency of high dose group were statistically higher than control and low dose group (P <0.05);in space exploration experiment,the du- ration time in target quadrant was statistically lower than control group (P <0.05).(3) There was no statistical differ- ence in dopamine (DA) content of striatum among all groups (P >0.05);the activity of acetylcholinesterase (AchE) was dose-dependently and statistically decreased in TDCPP-exposed groups compared with control group (P <0.05);the activity of superoxide dismutase (SOD) in high dose group was statistically decreased;the levels of glutathione (GSH) was statistically decreased in medium dose group and high dose group (P <0.05),which confirmed that TD- CPP induced oxidative stress in the brain of rats;the levels of inflammatory factors (TNF-α) in TDCPP-exposed groups were statistically increased compared with control group (P <0.05),which showed that TDCPP induced in- flammatory response in the brain of rats and caused

关 键 词：三(1 3-二氯-2-丙基)磷酸酯(TDCPP) 大鼠 神经毒性 氧化应激 炎症反应 

分 类 号：X171.5[环境科学与工程—环境科学]