李学彦;王思敏;周启星;邵晓东;张永国;胡献刚;

• 1:沈阳军区总医院消化科
• 2: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

摘要(Abstract)：

本研究观测有机磷酯阻燃剂(OPFRs)污染是否可以诱发肝脏损害,考察其发生及发展程度,并探讨其发生机理,为有机磷阻燃剂污染的防治和相关疾病的有效治疗提供基础数据和科学依据。实验以大鼠为动物模型,将60只SPF级SD雄性大鼠分为5组,每组12只,选取典型的氯代有机磷阻燃剂三(1,3-二氯-2-丙基)磷酸酯(TDCPP)对大鼠进行染毒,空白对照组不做任何处理,溶剂对照组以相同体积的橄榄油灌胃,染毒组以不同剂量的TDCPP进行灌胃(125 mg·kg^(-1)·d(-1)·d^(-1)、250 mg·kg(-1)、250 mg·kg^(-1)·d(-1)·d^(-1)和500 mg·kg(-1)和500 mg·kg^(-1)·d(-1)·d^(-1)),每周测量体重,于第4周和第8周取血检测肝功及其他生化指标,在第8周每组抽取3只大鼠取肝脏组织做HE染色,并用透射电镜观察分析肝组织病理学改变。TDCPP对大鼠染毒8周后,结果表明:(1)体重指标在灌胃1周后开始发生差异,TDCPP处理组大鼠的体重有下降的趋势,染毒组与空白对照组和溶剂对照组相比较,差异显著(*P<0.05,**P<0.01),其中高剂量灌胃组的体重下降最为明显(**P<0.01);(2)血清肝功指标表现出显著变化,血清谷丙转氨酶、谷草转氨酶、胆固醇和甘油三脂水平在第8周呈现明显下降趋势,染毒组与空白对照组和溶剂对照组比较,差异明显(*P<0.05,**P<0.01);(3) TDCPP暴露组生理生化指标变化明显,血清乙酰胆碱酯酶活性显著降低,MDA含量显著升高,SOD活力显著性降低,造成氧化损伤,与空白对照组和溶剂对照组比较,差异显著(*P<0.05,**P<0.01);(4)病理切片结果显示染毒组与对照组比较,细胞坏死现象明显,且高剂量组坏死更为严重。研究结果显示:TDCPP可引起大鼠体重明显下降,大鼠肝脏细胞损伤、合成功能下降,造成肝脏代谢功能紊乱,造成较为严重的肝损伤。

关键词(KeyWords)： 有机磷阻燃剂;TDCPP;大鼠;肝功损害;健康效应;病理改变

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(31670508)

作者(Authors): 李学彦;王思敏;周启星;邵晓东;张永国;胡献刚;

参考文献(References)：

• [1] van der Veen I,de Boer J. Phosphorus flame retardants:Properties,production,environmental occurrence,toxicity and analysis[J]. Chemosphere,2012,88(10):1119-1153
• [2] Marklund A,Andersson B,Haglund P. Organophosphorus flame retardants and plasticizers in air from various indoor environment[J]. Journal of Environmental Monitoring,2005,7(8):814-819
• [3] Marklund A,Andersson B,Haglund P,et al. Screening of organophosphorus compounds and their distribution in various indoor environments[J]. Chemosphere,2003,53(9):1137-1146
• [4] Stackelberg P E,Gibs J,Furlong E T,et al. Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds[J]. Science of the Total Environment,2007,377(2-3):255-272
• [5] Munoz-Quezada M T,Lucero B A,Barr D B,et al.Neurodevelopmental effects in children associated with exposure to organophosphate pesticides:A systematic review[J]. Neurotoxicology,2013,39:158-168
• [6] Wang Q,Lai N L S,Wang X,et al. Bioconcentration and transfer of the organophorous flame retardant 1,3-dichloro-2-propyl phosphate causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish larvae[J]. Environmental Science&Technology,2015,49(8):5123-5132
• [7] Farhat A,Buick J K,Williams A,et al. Tris(1,3-dichloro-2-propyl)phosphate perturbs the expression of genes involved in immune response and lipid and steroid metabolism in chicken embryos[J]. Toxicology and Applied Pharmacology,2014,275(2):104-112
• [8] Wang Q,Liang K,Liu J,et al. Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic–pituitary–thyroid axis[J]. Aquatic Toxicology,2013,126:207-213
• [9] Farhat A,Crump D,Chiu S,et al. In ovo effects of two organophosphate flame retardants—TCPP and TDCPP—on pipping success,development,mRNA expression,and thyroid hormone levels in chicken embryos[J].Toxicological Sciences,2013,134(1):92-102
• [10] Liu C S,Su G Y,Giesy J P,et al. Acute exposure to tris(1,3-dichloro-2-propyl)phosphate(TDCPP)causes hepatic inflammation and leads to hepatotoxicity in zebrafish[J]. Scientific Reports,2016,6(1):19045
• [11] Giannini E G,Testa R,Savarino V. Liver enzyme alteration:A guide for clinicians[J]. The Canadian Medical Association Journal,2005,172(3):367-379
• [12]张千,王取南.乙酰胆碱酯酶生物功能的研究进展及其应用[J].国外医学(卫生学分册),2008,35(3):143-147Zhang Q. Research progress and application of the biological function of acetylcholinesterase[J]. Journal of Medicine and Hygiene,2008,35(3):143-147(in Chinese)
• [13]周启星,赵梦阳,来子阳,等.有机磷阻燃剂的环境暴露与动物毒性效应[J].生态毒理学报,2017,12(5):1-11Zhou Q X,Zhao M Y,Lai Z Y,et al. Environmental exposure and animal toxicity effects of organophosphorus flame retardants[J]. Asian Journal of Ecotoxicology,2017,12(5):1-11(in Chinese)
• [14] Yuan L L,Li J S,Zha J M,et al. Targeting neurotrophic factors and their receptors,but not cholinesterase or neurotransmitter,in the neurotoxicity of TDCPP in Chinese rare minnow adults(Gobiocypris rarus)[J]. Environmental Pollution,2016,208:670-677
• [15] Arukwe A,Carteny C C,Eggen T,et al. Lipid peroxidation and oxidative stress responses in juvenile salmon exposed to waterborne levels of the organophosphate compounds tris(2-butoxyethyl)-and tris(2-chloroethyl)phosphates[J].Journal of Toxicology and Environmental Health-Part A Current Issues,2016,79(13-15):515-525
• [16] Arukwe A,Carteny C C,Moder M,et al. Differential modulation of neuro-and interrenal steroidogenesis of juvenile salmon by the organophosphates-tris(2-butoxyethyl)-and tris(2-cloroethyl)phosphate[J]. Environmental Research,2016,148:63-71
• [17] Chen G L,Jin Y X,Wu Y,et al. Exposure of male mice to two kinds of organophosphate flame retardants(OPFRs)induced oxidative stress and endocrine disruption[J]. Environmental Toxicology and Pharmacology,2015,40(1):310-318
• [18] Egloff C,Crump D,Porter E,et al. Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development,hepatic mRNA expression,thyroid hormone levels,and circulating bile acid concentrations in chicken embryos[J]. Toxicology and Applied Pharmacology,2014,279(3):303-310
• [19] Liu X S,Jung D,Jo A,et al. Long-term exposure to triphenylphosphate alters hormone balance and HPG,HPI,and HPT gene expression in zebrafish(Danio rerio)[J]. Environmental Toxicology and Chemistry,2016,35(9):2288-2296
• [20] Lesgards J F,Gauthier C,Iovanna J,et al. Effect of reactive oxygen and carbonyl species on crucial cellular antioxidant enzymes[J]. Chemico-Biological Interactions,2011,190(1):28-34
• [21] Lv Y J,Liu Z J,Tian Y J,et al. Effect on morphology,oxidative stress and energy metabolism enzymes in the testes of mice after a 13-week oral administration of melamine and cyanuric acid combination[J]. Regulatory Toxicology and Pharmacology,2013,65(2):183-188
• [22]周启星,孔繁翔,朱琳.主编.生态毒理学[M].北京:科学出版社,2004:20-30Zhou Q X,Kong F X,Zhu L.(eds.). Ecological Toxicology[M]. Beijing:Science Press,2004:20-30(in Chinese)