全氟辛烷磺酸对斑马鱼肝脏影响机制的代谢组学研究
|
摘要
为探究全氟辛烷磺酸(PFOS)对水生动物肝脏的慢性毒性毒害机制,寻找其肝脏慢性毒性相关的潜在标志物,运用气相色谱-质谱联用仪代谢组学方法研究暴露于PFOS中斑马鱼肝脏内源性代谢物的变化,寻找显著性差异代谢物及相关通路。实验分为4组:对照组及PFOS浓度分别为10、100、250μg·L~(-1)的实验组,每组20尾斑马鱼,实验时长40 d。结果显示,与对照组相比,PFOS浓度为10μg·L~(-1)的斑马鱼肝脏中筛选出4种发生显著性变化的代谢物,分别为牛磺酸、磷酸乙酰胺、β-D-葡萄糖、油酸,涉及4条代谢通路,即牛磺酸和亚牛磺酸代谢、鞘脂代谢、甘油磷脂代谢、糖酵解或葡萄糖生成。100μg·L~(-1)浓度组的斑马鱼肝脏中筛选出5种,包括牛磺酸、β-D-葡萄糖、棕榈酸、油酸、胆固醇,涉及5条代谢通路,即原代胆汁酸生物合成、牛磺酸和亚牛磺酸代谢、类固醇生物合成、类固醇激素生物合成、糖酵解或葡萄糖生成。250μg·L~(-1)浓度组的斑马鱼肝脏中筛选出5种,即牛磺酸、β-D-葡萄糖、乳酸、甘油-3-磷酸、磷酸乙酰胺,涉及5条代谢通路:牛磺酸和亚牛磺酸代谢、甘油磷脂代谢、甘油脂代谢、鞘脂代谢、糖酵解或葡萄糖生成。根据筛选出的差异代谢物生理功能和其涉及代谢通路分析,推测PFOS主要通过影响牛磺酸和亚牛磺酸代谢、糖酵解或葡萄糖生成及一些脂类代谢从而对斑马鱼肝脏产生毒性效应,其中牛磺酸、葡萄糖与油酸这3种代谢物可作为斑马鱼受PFOS胁迫肝脏代谢异常的潜在标记物。
In order to explore the mechanism of chronic toxicity of perfluorooctane sulfonate( PFOS) on livers of aquatic animals and to find potential markers related to chronic liver toxicity,a gas chromatography-mass spectrometry metabolomics method was used in this study,so as to study the effects of PFOS exposure on changes in liver endogenous metabolites and to discover metabolites that are of significant differences and their related pathways in Danio rerio. Four groups were set up including one control group and three experimental groups with PFOS concentration at 10,100 and 250 μg·L~(-1),respectively. 20 pieces of Danio rerio were cultured in each group,and the experiment lasted for 40 days. The results showed that compared with the control group,four metabolites including taurine,phosphoric acid amide,β-D-glucose and oleic acid were identified from the liver of Danio rerio of the group with PFOS concentration at 10 μg·L~(-1) and four metabolic pathways including taurine and hypotaurine metabolism,sphingolipid metabolism,glycerophospholipid metabolism,and glycolysis or gluconeogenesis were involved. Five metabolites including taurine,β-D-glucose,palmitic acid,oleic acid and cholesterol,were identified from the liver of zebrafish of the group with PFOS concentration at 100 μg·L~(-1),and five metabolic pathways including primary bile acid biosynthesis,taurine and hypotaurine metabolism,steroid biosynthesis,steroid hormone biosynthesis and glycolysis or gluconeogenesis were involved. Four metabolites including taurine,β-D-glucose,lactic acid,glycerol-3-phosphate and phosphoacetamide,were identified from the liver of Danio rerio group with PFOS concentration at250 μg·L~(-1),and five metabolic pathways including taurine and hypotaurine metabolism,glycerophospholipid metabolism,glycerolipid metabolism,sphingolipid metabolism and glycolysis or gluconeogenesis were invloved. Based on the physiological functions of the identified metabolites and the analysis of their metabolic pathways,it was speculated that PFOS exerts toxic effects on Danio rerio liver mainly by interfering the metabolic pathways of taurine and hypotaurine,glycolysis or glucose production,and some lipid metabolism. Among them,the three metabolites including taurine,glucose and oleic acid can be used as potential markers for Danio rerio liver metabolism abnormalities induced by PFOS.
In order to explore the mechanism of chronic toxicity of perfluorooctane sulfonate( PFOS) on livers of aquatic animals and to find potential markers related to chronic liver toxicity,a gas chromatography-mass spectrometry metabolomics method was used in this study,so as to study the effects of PFOS exposure on changes in liver endogenous metabolites and to discover metabolites that are of significant differences and their related pathways in Danio rerio. Four groups were set up including one control group and three experimental groups with PFOS concentration at 10,100 and 250 μg·L~(-1),respectively. 20 pieces of Danio rerio were cultured in each group,and the experiment lasted for 40 days. The results showed that compared with the control group,four metabolites including taurine,phosphoric acid amide,β-D-glucose and oleic acid were identified from the liver of Danio rerio of the group with PFOS concentration at 10 μg·L~(-1) and four metabolic pathways including taurine and hypotaurine metabolism,sphingolipid metabolism,glycerophospholipid metabolism,and glycolysis or gluconeogenesis were involved. Five metabolites including taurine,β-D-glucose,palmitic acid,oleic acid and cholesterol,were identified from the liver of zebrafish of the group with PFOS concentration at 100 μg·L~(-1),and five metabolic pathways including primary bile acid biosynthesis,taurine and hypotaurine metabolism,steroid biosynthesis,steroid hormone biosynthesis and glycolysis or gluconeogenesis were involved. Four metabolites including taurine,β-D-glucose,lactic acid,glycerol-3-phosphate and phosphoacetamide,were identified from the liver of Danio rerio group with PFOS concentration at250 μg·L~(-1),and five metabolic pathways including taurine and hypotaurine metabolism,glycerophospholipid metabolism,glycerolipid metabolism,sphingolipid metabolism and glycolysis or gluconeogenesis were invloved. Based on the physiological functions of the identified metabolites and the analysis of their metabolic pathways,it was speculated that PFOS exerts toxic effects on Danio rerio liver mainly by interfering the metabolic pathways of taurine and hypotaurine,glycolysis or glucose production,and some lipid metabolism. Among them,the three metabolites including taurine,glucose and oleic acid can be used as potential markers for Danio rerio liver metabolism abnormalities induced by PFOS.
引文
[1] Paul A G,Jones K C,Sweetman A J. A first global production,emission,and environmental inventory for perfluorooctane sulfonate[J]. Environmental Science&Technology,2009,43(2):386-392
[2]张德勇,许晓路.全氟辛烷磺酰基化合物(PFOS)类有机污染物在生物体中的污染现状[J].生态毒理学报,2010,5(5):639-646Zhang D Y,Xu X L. Review on perfluorooctane sulphonate(PFOS)contamination of organisms[J]. Asian Journal of Ecotoxicology,2010,5(5):639-646(in Chinese)
[3]梅胜放.我国PFOS/PFOA的生产、应用以及国内外标准现状[J].有机氟工业,2008(1):21-25
[4]李志芬,马太玲,史雅娟.持久性有机污染物全氟辛烷磺酸PFOS污染生态环境研究进展[J].山东农业大学学报:自然科学版,2015,46(2):204-210Li Z F,Ma T L,Shi Y J. A review for the studies on polluting ecological environment of the persistent organic pollutant perfluorooctane sulfonate(PFOS)[J]. Journal of Shandong Agricultural University:Natural Science Edition,2015,46(2):204-210(in Chinese)
[5]江敏,袁璐瑶.全氟辛烷磺酸(PFOS)的环境污染及生态毒性研究进展[J].安全与环境学报,2014,14(4):207-212Jiang M,Yuan L Y. Research advances on the environmental pollution and ecological toxic harm of the perfluorooctane sulfonate(PFOS)[J]. Journal of Safety and Environment,2014,14(4):207-212(in Chinese)
[6]宋薇,山香菊,王燕丽,等.超高效液相色谱-串联质谱法测定北京市区灰霾天气空气颗粒物中的全氟化合物[J].现代科学仪器,2014(3):149-157Song W,Shan X J,Wang Y L,et al. Determination of perfluorinated compounds in airborne Beijing urban area by ultra high performance liquid spectrometry particulate matter of haze in chromatography-tandem mass[J]. Modern Scientific Instruments,2014(3):149-157(in Chinese)
[7] Munoz G,Labadie P,Botta F,et al. Occurrence survey and spatial distribution of perfluoroalkyl and polyfluoroalkyl surfactants in groundwater, surface water, and sediments from tropical environments[J]. Science of the Total Environment,2017,607:243-252
[8] Zhao Z,Tang J H,Mi L J,et al. Perfluoroalkyl and polyfluoroalkyl substances in the lower atmosphere and surface waters of the Chinese Bohai Sea,Yellow Sea,and Yangtze River Estuary[J]. Science of the Total Environment,2017,599:114-123
[9]李杰,高月,王之芬,等.汉江水体和沉积物中全氟化合物的风险评估[J].北京大学学报:自然科学版,2017,53(5):913-920Li J,Gao Y,Wang Z F,et al. Risk assessment of perfluoroalkyl compounds(PFCs)in water and sediment samples of Hanjiang River[J]. Acta Scientiarum Naturalium Universitatis Pekinensis,2017,53(5):913-920(in Chinese)
[10] Becker A M,Gerstmann S,Frank H. Perfluorooctanoic acid and perfluorooctane sulfonate in the sediment of the Roter Main River,Bayreuth,Germany[J]. Environmental Pollution,2008,156(3):818-820
[11] Christensen K Y,Thompson B A,Werner M,et al.Levels of persistent contaminants in relation to fish consumption among older male anglers in Wisconsin[J].International Journal of Hygiene and Environmental Health,2016,219(2):184-194
[12] Sinclair E,Mayack D T,Roblee K,et al. Occurrence of perfluoroalkyl surfactants in water,fish,and birds from New York State[J]. Archives of Environmental Contamination and Toxicology,2006,50(3):398-410
[13] Ehresman D J,Froehlich J W,Olsen G W,et al. Comparison of human whole blood,plasma,and serum matrices for the determination of perfluorooctane sulfonate(PFOS),perfluorooctanoate(PFOA),and other fluorochemicals[J]. Environmental Research,2007,103(2):176-184
[14]高珂,傅建捷,高燕,等.武汉市某高校学生血清中全氟烷酸水平及暴露途径初步研究[J].环境化学,2015,34(8):1424-1432Gao K,Fu J J,Gao Y,et al. A preliminary study on perfluoroalkyl acids levels in serum and exposure pathways for students from a university in Wuhan[J]. Environmental Chemistry,2015,34(8):1424-1432(in Chinese)
[15] Volkel W,Mosch C,Kiranoglu M,et al. Perfluorinated compounds(PFC)in human breast milk[J]. Toxicology Letters,2009,189(Suppl):151-152
[16]金一和,刘晓,李彤,等.沈阳地区成人血清和脐带血中全氟有机物污染现状[J].卫生研究,2004,33(4):481-483Jin Y H,Liu X,Li T,et al. Status of perfluorochemicals in adult serum and umbilical blood in Shenyang[J]. Journal of Hygiene Research,2004,33(4):481-483(in Chinese)
[17]刘晓晖,胡宏,李双月.全氟辛烷磺酸神经发育毒性机制研究进展[J].生态毒理学报,2013,8(5):643-649Liu X H,Hu H,Li S Y,et al. Research progress on mechanisms in the developmental neurotoxicity of PFOS[J]. Asian Journal of Ecotoxicology,2013,8(5):643-649(in Chinese)
[18]万延建. PFOS的肝脏和心脏发育毒性研究[D].武汉:华中科技大学,2010:2-5Wan Y J. Study on liver and cardio developmental toxicity of PFOS[D]. Wuhan:Huazhong University of Science and Technology,2010:2-5(in Chinese)
[19] Chen T,Zhang L,Yue J Q,et al. Prenatal PFOS exposure induces oxidative stress and apoptosis in the lung of rat offspring[J]. Reproductive Toxicology,2012,33(4):538-545
[20] Corsini E,Luebke R W,Germolec D R,et al. Perfluorinated compounds:Emerging POPs with potential immunotoxicity[J]. Toxicology Letters,2014,230(2):263-270
[21] Zhang Y H,Wang J,Dong G H,et al. Mechanism of perfluorooctane sulfonate(PFOS)-induced apoptosis in the immunocyte[J]. Journal of Immunotoxicology,2013,10(1):49-58
[21]赵雪松,任新,段小月,等.全氟辛烷磺酸盐暴露对斑马鱼胚胎发育毒性与氧化应激的影响[J].唐山学院学报,2016,29(6):12-16Zhao X S,Ren X,Duan X Y,et al. On the effect of PFOS on developmental toxicity and oxidative stress in zebrafish embryos[J]. Journal of Tangshan College,2016,29(6):12-16(in Chinese)
[22] Lai K P,Li J W,Cheung A,et al. Transcriptome sequencing reveals prenatal PFOS exposure on liver disorders[J]. Environmental Pollution,2017,223:416-425
[23]徐仙.孕哺期PFOS暴露对子代肝糖代谢影响及机制研究[D].乌鲁木齐:新疆医科大学,2015:6-31Xu X. The study of effects and mechanism of perinatal PFOS exposure on hepatic glucose metabolism of rats[D]. Urumqi:Xinjiang Medical University,2015:6-31(in Chinese)
[24]刘清国.全氟辛烷磺酸对大鼠的肝肾毒性及番茄红素的保护作用[D].衡阳:南华大学,2010:4-27Liu Q G. The study of PFOS’s hepatorenal toxicity and lycopene’s protection function in rats[D]. Hengyang:University of South China,2010:4-27(in Chinese)
[25]潘若雷,杨淑雯,江敏.全氟辛烷磺酸(PFOS)对三角帆蚌肝胰腺的氧化性损伤[J].生态毒理学报,2016,11(6):112-120Pan R L,Yang S W,Jiang M. Perfluorooctane sulfonate(PFOS)-induced oxidative damage in hepatopancreas of Hyriopsis cumingii[J]. Asian Journal of Ecotoxicology,2016,11(6):112-120(in Chinese)
[26]王玲.全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)干扰BALB/c小鼠脂类代谢效应研究[D].武汉:华中农业大学,2011:26-29Wang L. Disturbance effect of perfluorooctane sulfonate and perfluorooctanoic acid on lipid metabolism in BALB/c mice[D]. Wuhan:Huazhong Agricultural University,2011:26-29(in Chinese)
[27]党红蕾,那广水,高会,等.全氟辛烷磺酸(PFOS)对半滑舌鳎肝脏细胞的毒性效应[J].生态毒理学报,2015,10(4):162-169Dang H L,Na G S,Gao H,et al. Toxicity effects of perfluorooctane sulfonate(PFOS)on liver cells of Cynoglossus semilaevis[J]. Asian Journal of Ecotoxicology,2015,10(4):162-169(in Chinese)
[28]杜智,刘树业,刘运德主编.临床代谢组学[M].天津:天津科技翻译出版有限公司,2013:1-2
[29] Tang H R,Wang Y L. Metabonomics:A revolution in progress[J]. Progress in Biochemistry and Biophysics,2006,33(5):401-417
[30] Kariuki M N,Nagato E G,Lankadurai B P,et al. Analysis of sub-lethal toxicity of perfluorooctane sulfonate(PFOS)to Daphnia magna using1H nuclear magnetic resonancebased metabolomics[J]. Metabolites,2017,7(2):1-13
[31] Yu N Y,Wei S,Li M Y,et al. Effects of perfluorooctanoic acid on metabolic profiles in brain and liver of mouse revealed by a high-throughput targeted metabolomics approach[J]. Scientific Reports,2016,6:1-10
[32]孙启慧,张静,李壮壮,等.基于代谢组学的麻黄细辛附子汤治疗流感小鼠的作用机制研究[J].中国中药杂志,2017,42(4):763-771Sun Q H,Zhang J,Li Z Z,et al. Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information[J]. China Journal of Chinese Materia Medica,2017,42(4):763-771(in Chinese)
[33]龚梦鹃,巫圣乾,岳贺,等.基于1H-NMR护肝片抗大鼠急性肝损伤的代谢组学研究[J].中国药理学通报,2017,33(12):1766-1770Gong M J,Wu S Q,Yue H,et al. Metabonomic analysis of Hugan Tablets on CCl4induced acute hepatic injury in rats based on 1H-NMR[J]. Chinese Pharmacological Bulletin,2017,33(12):1766-1770(in Chinese)
[34]苟小军,梁薇,刘志丹,等.过敏性鼻炎患者血液代谢组学研究[J].中国医院药学杂志,2017,37(18):1777-1782Gou X J,Liang W,Liu Z D,et al. Study on serum metabolomics of patients with allergic rhinitis[J]. Chinese Journal of Hospital Pharmacy,2017,37(18):1777-1782(in Chinese)
[35] Du H L,Wang K Q,Su L,et al. Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression[J]. Journal of Pharmaceutical and Biomedical Analysis,2016,128:469-479
[36] Bollard M E,Keun H C,Beckonert O,et al. Comparative metabonomics of differential hydrazine toxicity in the rat and mouse[J]. Toxicology and Applied Pharmacology,2005,204(2):135-151
[37] Qi L,Cao C,Hu L,et al. Metabonomic analysis of the protective effect of quercetin on the toxicity induced by mixture of organophosphate pesticides in rat urine[J]. Human&Experimental Toxicology,2017,36(5):494-507
[38] Zhou L L,Zhang W P,Xie W P,et al. Tributyl phosphate impairs the urea cycle and alters liver pathology and metabolism in mice after short-term exposure based on a metabonomics study[J]. Science of the Total Environment,2017,603-604:77-85
[39] Zheng R,Yang Y H,Wen Y M,et al. Metabolomic analysis of amino acid and fat metabolism in rats with Ltryptophan supplementation[J]. Amino Acids,2014,46(12):2681-2691
[40] Yang Y X,Zheng N,Zhao X W,et al. Metabolomic biomarkers identify differences in milk produced by Holstein cows and other minor dairy animals[J]. Journal of Proteomics,2016,136(16):174-182
[41]胡芹.全氟辛烷磺酸(PFOS)对斑马鱼胚胎发育及成鱼的毒性效应研究[D].武汉:华中农业大学,2009:30-43Hu Q. Embryo developmental and maternal toxicity of perfluorooctane sulfonate(PFOS)in the zebrafish[D].Wuhan:Huazhong Agricultural University,2009:30-43(in Chinese)
[42]崔燕.全氟辛烷磺酸对斑马鱼脂代谢和糖代谢毒理作用研究[D].温州:温州医学院,2012:12-22Cui Y. Altered lipid metabolism and glucose metabolism in zebrafish exposed to perfluorooctane sulphonic acid[D]. Wenzhou:Wenzhou Medical University,2012:12-22(in Chinese)
[43]王镜岩等主编.生物化学下[M].北京:高等教育出版社,2002:80-336
[44]徐贵发,蔺新英主编.功能食品与功能因子[M].济南:山东大学出版社,2005:255-258
[45] Li C N,Liu X H,Liu Q,et al. Protection of taurine against PFOS-induced neurotoxicity in PC12 cells[J].Advances in Experimental Medicine&Biology,2017,975(10):907-916
[46] Tsuda S. Differential toxicity between perfluorooctane sulfonate(PFOS)and perfluorooctanoic acid(PFOA)[J]. Journal of Toxicological Sciences,2016,41:27-36
[47] Faubert B,Li K Y,Cai L,et al. Lactate metabolism in human lung tumors[J]. Cell,2017,171(2):358-371
[48] Wu H,Ding Z,Hu D,et al. Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death[J]. The Journal of Pathology,2012,227(10):189-199
[49] Xie J,Wu H,Dai C,et al. Beyond Warburg effect-dual metabolic nature of cancer cells[J]. Scientific Reports,2014,4:1-12
[50] Chao M,Wu H,Jin K,et al. A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis[J].Elife,2016,5:1-18
[51]张敏,秦鑫,张文静,等. NAD+分子在癌症细胞生物学中的重要地位[J].现代生物医学进展,2015,15(32):6393-6397Zhang M,Qin X,Zhang W J,et al. NAD+:The key molecule in cancer cell biology[J]. Progress in Modern Biomedicine,2015,15(32):6393-6397(in Chinese)
[52]彭超,黄和,肖爱华,等.代谢组学分析技术平台及方法研究进展[J].食品科技,2008,33(9):220-223Peng C,Huang H,Xiao A H,et al. Progress of metabolomics analytical platform and methodologies[J]. Food Science and Technology,2008,33(9):220-223(in Chinese)
[53] Moco S,Bino R J,Vorst O,et al. A liquid chromatography-mass spectrometry-based metabolome database for tomato[J]. Physiologia Plantarum,2006,41(4):1205-1218
[2]张德勇,许晓路.全氟辛烷磺酰基化合物(PFOS)类有机污染物在生物体中的污染现状[J].生态毒理学报,2010,5(5):639-646Zhang D Y,Xu X L. Review on perfluorooctane sulphonate(PFOS)contamination of organisms[J]. Asian Journal of Ecotoxicology,2010,5(5):639-646(in Chinese)
[3]梅胜放.我国PFOS/PFOA的生产、应用以及国内外标准现状[J].有机氟工业,2008(1):21-25
[4]李志芬,马太玲,史雅娟.持久性有机污染物全氟辛烷磺酸PFOS污染生态环境研究进展[J].山东农业大学学报:自然科学版,2015,46(2):204-210Li Z F,Ma T L,Shi Y J. A review for the studies on polluting ecological environment of the persistent organic pollutant perfluorooctane sulfonate(PFOS)[J]. Journal of Shandong Agricultural University:Natural Science Edition,2015,46(2):204-210(in Chinese)
[5]江敏,袁璐瑶.全氟辛烷磺酸(PFOS)的环境污染及生态毒性研究进展[J].安全与环境学报,2014,14(4):207-212Jiang M,Yuan L Y. Research advances on the environmental pollution and ecological toxic harm of the perfluorooctane sulfonate(PFOS)[J]. Journal of Safety and Environment,2014,14(4):207-212(in Chinese)
[6]宋薇,山香菊,王燕丽,等.超高效液相色谱-串联质谱法测定北京市区灰霾天气空气颗粒物中的全氟化合物[J].现代科学仪器,2014(3):149-157Song W,Shan X J,Wang Y L,et al. Determination of perfluorinated compounds in airborne Beijing urban area by ultra high performance liquid spectrometry particulate matter of haze in chromatography-tandem mass[J]. Modern Scientific Instruments,2014(3):149-157(in Chinese)
[7] Munoz G,Labadie P,Botta F,et al. Occurrence survey and spatial distribution of perfluoroalkyl and polyfluoroalkyl surfactants in groundwater, surface water, and sediments from tropical environments[J]. Science of the Total Environment,2017,607:243-252
[8] Zhao Z,Tang J H,Mi L J,et al. Perfluoroalkyl and polyfluoroalkyl substances in the lower atmosphere and surface waters of the Chinese Bohai Sea,Yellow Sea,and Yangtze River Estuary[J]. Science of the Total Environment,2017,599:114-123
[9]李杰,高月,王之芬,等.汉江水体和沉积物中全氟化合物的风险评估[J].北京大学学报:自然科学版,2017,53(5):913-920Li J,Gao Y,Wang Z F,et al. Risk assessment of perfluoroalkyl compounds(PFCs)in water and sediment samples of Hanjiang River[J]. Acta Scientiarum Naturalium Universitatis Pekinensis,2017,53(5):913-920(in Chinese)
[10] Becker A M,Gerstmann S,Frank H. Perfluorooctanoic acid and perfluorooctane sulfonate in the sediment of the Roter Main River,Bayreuth,Germany[J]. Environmental Pollution,2008,156(3):818-820
[11] Christensen K Y,Thompson B A,Werner M,et al.Levels of persistent contaminants in relation to fish consumption among older male anglers in Wisconsin[J].International Journal of Hygiene and Environmental Health,2016,219(2):184-194
[12] Sinclair E,Mayack D T,Roblee K,et al. Occurrence of perfluoroalkyl surfactants in water,fish,and birds from New York State[J]. Archives of Environmental Contamination and Toxicology,2006,50(3):398-410
[13] Ehresman D J,Froehlich J W,Olsen G W,et al. Comparison of human whole blood,plasma,and serum matrices for the determination of perfluorooctane sulfonate(PFOS),perfluorooctanoate(PFOA),and other fluorochemicals[J]. Environmental Research,2007,103(2):176-184
[14]高珂,傅建捷,高燕,等.武汉市某高校学生血清中全氟烷酸水平及暴露途径初步研究[J].环境化学,2015,34(8):1424-1432Gao K,Fu J J,Gao Y,et al. A preliminary study on perfluoroalkyl acids levels in serum and exposure pathways for students from a university in Wuhan[J]. Environmental Chemistry,2015,34(8):1424-1432(in Chinese)
[15] Volkel W,Mosch C,Kiranoglu M,et al. Perfluorinated compounds(PFC)in human breast milk[J]. Toxicology Letters,2009,189(Suppl):151-152
[16]金一和,刘晓,李彤,等.沈阳地区成人血清和脐带血中全氟有机物污染现状[J].卫生研究,2004,33(4):481-483Jin Y H,Liu X,Li T,et al. Status of perfluorochemicals in adult serum and umbilical blood in Shenyang[J]. Journal of Hygiene Research,2004,33(4):481-483(in Chinese)
[17]刘晓晖,胡宏,李双月.全氟辛烷磺酸神经发育毒性机制研究进展[J].生态毒理学报,2013,8(5):643-649Liu X H,Hu H,Li S Y,et al. Research progress on mechanisms in the developmental neurotoxicity of PFOS[J]. Asian Journal of Ecotoxicology,2013,8(5):643-649(in Chinese)
[18]万延建. PFOS的肝脏和心脏发育毒性研究[D].武汉:华中科技大学,2010:2-5Wan Y J. Study on liver and cardio developmental toxicity of PFOS[D]. Wuhan:Huazhong University of Science and Technology,2010:2-5(in Chinese)
[19] Chen T,Zhang L,Yue J Q,et al. Prenatal PFOS exposure induces oxidative stress and apoptosis in the lung of rat offspring[J]. Reproductive Toxicology,2012,33(4):538-545
[20] Corsini E,Luebke R W,Germolec D R,et al. Perfluorinated compounds:Emerging POPs with potential immunotoxicity[J]. Toxicology Letters,2014,230(2):263-270
[21] Zhang Y H,Wang J,Dong G H,et al. Mechanism of perfluorooctane sulfonate(PFOS)-induced apoptosis in the immunocyte[J]. Journal of Immunotoxicology,2013,10(1):49-58
[21]赵雪松,任新,段小月,等.全氟辛烷磺酸盐暴露对斑马鱼胚胎发育毒性与氧化应激的影响[J].唐山学院学报,2016,29(6):12-16Zhao X S,Ren X,Duan X Y,et al. On the effect of PFOS on developmental toxicity and oxidative stress in zebrafish embryos[J]. Journal of Tangshan College,2016,29(6):12-16(in Chinese)
[22] Lai K P,Li J W,Cheung A,et al. Transcriptome sequencing reveals prenatal PFOS exposure on liver disorders[J]. Environmental Pollution,2017,223:416-425
[23]徐仙.孕哺期PFOS暴露对子代肝糖代谢影响及机制研究[D].乌鲁木齐:新疆医科大学,2015:6-31Xu X. The study of effects and mechanism of perinatal PFOS exposure on hepatic glucose metabolism of rats[D]. Urumqi:Xinjiang Medical University,2015:6-31(in Chinese)
[24]刘清国.全氟辛烷磺酸对大鼠的肝肾毒性及番茄红素的保护作用[D].衡阳:南华大学,2010:4-27Liu Q G. The study of PFOS’s hepatorenal toxicity and lycopene’s protection function in rats[D]. Hengyang:University of South China,2010:4-27(in Chinese)
[25]潘若雷,杨淑雯,江敏.全氟辛烷磺酸(PFOS)对三角帆蚌肝胰腺的氧化性损伤[J].生态毒理学报,2016,11(6):112-120Pan R L,Yang S W,Jiang M. Perfluorooctane sulfonate(PFOS)-induced oxidative damage in hepatopancreas of Hyriopsis cumingii[J]. Asian Journal of Ecotoxicology,2016,11(6):112-120(in Chinese)
[26]王玲.全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)干扰BALB/c小鼠脂类代谢效应研究[D].武汉:华中农业大学,2011:26-29Wang L. Disturbance effect of perfluorooctane sulfonate and perfluorooctanoic acid on lipid metabolism in BALB/c mice[D]. Wuhan:Huazhong Agricultural University,2011:26-29(in Chinese)
[27]党红蕾,那广水,高会,等.全氟辛烷磺酸(PFOS)对半滑舌鳎肝脏细胞的毒性效应[J].生态毒理学报,2015,10(4):162-169Dang H L,Na G S,Gao H,et al. Toxicity effects of perfluorooctane sulfonate(PFOS)on liver cells of Cynoglossus semilaevis[J]. Asian Journal of Ecotoxicology,2015,10(4):162-169(in Chinese)
[28]杜智,刘树业,刘运德主编.临床代谢组学[M].天津:天津科技翻译出版有限公司,2013:1-2
[29] Tang H R,Wang Y L. Metabonomics:A revolution in progress[J]. Progress in Biochemistry and Biophysics,2006,33(5):401-417
[30] Kariuki M N,Nagato E G,Lankadurai B P,et al. Analysis of sub-lethal toxicity of perfluorooctane sulfonate(PFOS)to Daphnia magna using1H nuclear magnetic resonancebased metabolomics[J]. Metabolites,2017,7(2):1-13
[31] Yu N Y,Wei S,Li M Y,et al. Effects of perfluorooctanoic acid on metabolic profiles in brain and liver of mouse revealed by a high-throughput targeted metabolomics approach[J]. Scientific Reports,2016,6:1-10
[32]孙启慧,张静,李壮壮,等.基于代谢组学的麻黄细辛附子汤治疗流感小鼠的作用机制研究[J].中国中药杂志,2017,42(4):763-771Sun Q H,Zhang J,Li Z Z,et al. Action mechanism of Mahuang Xixin Fuzi decoction for mice with influenza based on metabolomics information[J]. China Journal of Chinese Materia Medica,2017,42(4):763-771(in Chinese)
[33]龚梦鹃,巫圣乾,岳贺,等.基于1H-NMR护肝片抗大鼠急性肝损伤的代谢组学研究[J].中国药理学通报,2017,33(12):1766-1770Gong M J,Wu S Q,Yue H,et al. Metabonomic analysis of Hugan Tablets on CCl4induced acute hepatic injury in rats based on 1H-NMR[J]. Chinese Pharmacological Bulletin,2017,33(12):1766-1770(in Chinese)
[34]苟小军,梁薇,刘志丹,等.过敏性鼻炎患者血液代谢组学研究[J].中国医院药学杂志,2017,37(18):1777-1782Gou X J,Liang W,Liu Z D,et al. Study on serum metabolomics of patients with allergic rhinitis[J]. Chinese Journal of Hospital Pharmacy,2017,37(18):1777-1782(in Chinese)
[35] Du H L,Wang K Q,Su L,et al. Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression[J]. Journal of Pharmaceutical and Biomedical Analysis,2016,128:469-479
[36] Bollard M E,Keun H C,Beckonert O,et al. Comparative metabonomics of differential hydrazine toxicity in the rat and mouse[J]. Toxicology and Applied Pharmacology,2005,204(2):135-151
[37] Qi L,Cao C,Hu L,et al. Metabonomic analysis of the protective effect of quercetin on the toxicity induced by mixture of organophosphate pesticides in rat urine[J]. Human&Experimental Toxicology,2017,36(5):494-507
[38] Zhou L L,Zhang W P,Xie W P,et al. Tributyl phosphate impairs the urea cycle and alters liver pathology and metabolism in mice after short-term exposure based on a metabonomics study[J]. Science of the Total Environment,2017,603-604:77-85
[39] Zheng R,Yang Y H,Wen Y M,et al. Metabolomic analysis of amino acid and fat metabolism in rats with Ltryptophan supplementation[J]. Amino Acids,2014,46(12):2681-2691
[40] Yang Y X,Zheng N,Zhao X W,et al. Metabolomic biomarkers identify differences in milk produced by Holstein cows and other minor dairy animals[J]. Journal of Proteomics,2016,136(16):174-182
[41]胡芹.全氟辛烷磺酸(PFOS)对斑马鱼胚胎发育及成鱼的毒性效应研究[D].武汉:华中农业大学,2009:30-43Hu Q. Embryo developmental and maternal toxicity of perfluorooctane sulfonate(PFOS)in the zebrafish[D].Wuhan:Huazhong Agricultural University,2009:30-43(in Chinese)
[42]崔燕.全氟辛烷磺酸对斑马鱼脂代谢和糖代谢毒理作用研究[D].温州:温州医学院,2012:12-22Cui Y. Altered lipid metabolism and glucose metabolism in zebrafish exposed to perfluorooctane sulphonic acid[D]. Wenzhou:Wenzhou Medical University,2012:12-22(in Chinese)
[43]王镜岩等主编.生物化学下[M].北京:高等教育出版社,2002:80-336
[44]徐贵发,蔺新英主编.功能食品与功能因子[M].济南:山东大学出版社,2005:255-258
[45] Li C N,Liu X H,Liu Q,et al. Protection of taurine against PFOS-induced neurotoxicity in PC12 cells[J].Advances in Experimental Medicine&Biology,2017,975(10):907-916
[46] Tsuda S. Differential toxicity between perfluorooctane sulfonate(PFOS)and perfluorooctanoic acid(PFOA)[J]. Journal of Toxicological Sciences,2016,41:27-36
[47] Faubert B,Li K Y,Cai L,et al. Lactate metabolism in human lung tumors[J]. Cell,2017,171(2):358-371
[48] Wu H,Ding Z,Hu D,et al. Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death[J]. The Journal of Pathology,2012,227(10):189-199
[49] Xie J,Wu H,Dai C,et al. Beyond Warburg effect-dual metabolic nature of cancer cells[J]. Scientific Reports,2014,4:1-12
[50] Chao M,Wu H,Jin K,et al. A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis[J].Elife,2016,5:1-18
[51]张敏,秦鑫,张文静,等. NAD+分子在癌症细胞生物学中的重要地位[J].现代生物医学进展,2015,15(32):6393-6397Zhang M,Qin X,Zhang W J,et al. NAD+:The key molecule in cancer cell biology[J]. Progress in Modern Biomedicine,2015,15(32):6393-6397(in Chinese)
[52]彭超,黄和,肖爱华,等.代谢组学分析技术平台及方法研究进展[J].食品科技,2008,33(9):220-223Peng C,Huang H,Xiao A H,et al. Progress of metabolomics analytical platform and methodologies[J]. Food Science and Technology,2008,33(9):220-223(in Chinese)
[53] Moco S,Bino R J,Vorst O,et al. A liquid chromatography-mass spectrometry-based metabolome database for tomato[J]. Physiologia Plantarum,2006,41(4):1205-1218