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化学进展 2021, Vol. 33 Issue (4): 503-511 DOI: 10.7536/PC201240   后一篇

• 综述 •

基于质谱成像和组学分析的环境毒理研究

赵超1,2, 蔡宗苇1,*()   

  1. 1 香港浸会大学 环境与生物分析国家重点实验室 香港 999077
    2 中国科学院深圳先进技术研究院 生物医学与健康工程研究所 深圳 518000
  • 收稿日期:2020-12-24 修回日期:2021-02-25 出版日期:2021-04-20 发布日期:2021-02-25
  • 通讯作者: 蔡宗苇
  • 基金资助:
    科技部港澳台科技创新合作重点专项(2017YFE0191000)
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Mass Spectrometry Imaging and Omics for Environmental Toxicology Research

Chao Zhao1,2, Zongwei Cai1()   

  1. 1 State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong 999077, China
    2 Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
  • Received:2020-12-24 Revised:2021-02-25 Online:2021-04-20 Published:2021-02-25
  • Contact: Zongwei Cai
  • Supported by:
    the key innovation project from Ministry of Science and Technology of China(2017YFE0191000)

生物体多器官的空间异质性导致环境污染物在生物体内的毒性分子机制错综复杂。基于传统化学和生物分析的环境毒理学研究,通常将研究对象看作“均一”整体,无法从空间上准确定位污染物及其代谢。以质谱成像和组学分析为基础的技术,同时对污染物、污染物代谢活化途径及其诱导的生物分子进行定性、定量和空间分析,从而确定污染物迁移、生物学效应及其毒性作用的靶器官,是目前最有前景的分析方法之一。本文综述了质谱成像和组学研究策略和特征,介绍了本课题组在相关领域取得的研究进展。同时简单展望了单细胞质谱成像、微流控芯片-质谱成像联合策略等先进技术在环境毒理研究中的潜在应用。

关键词： 质谱成像, 质谱组学分析, 环境毒性, 生物标志物, 毒性效应

The spatial heterogeneity of multiple organs causes the complexity of the molecular mechanism in environmental pollutant-exposed organisms. The conventional environmental toxicology research based on chemical and biological analysis has been considered as a “homogeneous” whole, which is difficult to locate the pollutant and its metabolism in spatial level. As one of the most promising analytical method, mass spectrometry imaging(MSI) combined with mass spectrometry-based omics has been applied for the qualitative, quantitative and spatial localization analysis of pollutant and its metabolic activation pathways as well as biomolecule variation, allowing the screening of pollutant exposure-related target organs and investigation of the migration and biological effects of pollutants. Herein, we summarize the strategies and characteristics of MSI and omics in environmental toxicology. The future development and challenges are also prospected, including the single cell imaging, and the integrated microfluidic chip-MSI technique.

Contents

1 Introduction

2 MSI and omics analysis

2.1 Pollutant exposed experimental models

2.2 Pollutant exposed histological analysis

2.3 MSI and omics-based environmental toxicology research

2.4 Exploration of toxicological mechanisms

3 Toxicity research of typical pollutants

3.1 Bisphenols

3.2 PM2.5

3.3 Other applications

4 Conclusion and perspective

Key words: mass spectrometry imaging, mass spectrometry-based omics, environmental toxicology, biomarkers, toxicological effects
()
图1 基于MSI和组学分析的环境毒理研究策略
Fig.1 Research strategy of MSI and omics analysis in environmental toxicology
图2 环境暴露对大鼠乳腺发育的影响[23](组织病理来自HE染色,10倍放大)
Fig.2 Effects of environmental exposure on mammary gland(MG) development in rats[23](Histological figures are derived from HE staining, 10×). Copyright 2011, Environmental Health Perspectives
图3 MSI技术中空间分辨率的比较[28](a,常规方法;b,激光为基础的高分辨率成像方法。LDI,激光解吸电离;fs-LDPI,飞秒激光解吸和激光后电离;EUV,极紫外;NDPI,近场解吸后电离;TEAI,尖端增强消融电离)
Fig.3 Comparison of spatial resolution in MSI[28](LDI, laser desorption ionization; fs-LDPI, fs laser desorption with laser post-ionization; EUV, extreme ultraviolet; NDPI, near-field desorption post-ionization; TEAI, tip-enhanced ablation and ionization) Copyright 2019, American Chemical Society
图4 MSI和显微镜图片融合技术应用举例[37]
Fig.4 Application example of MSI-microscopy fusion[37]. Copyright 2014, Springer Nature
图5 BPS诱导小鼠肾脏毒性的脂质代谢网络变化[60]
Fig.5 Variation of lipid metabolism network in BPS-exposed kidney in mice model[60]. Copyright 2018, American Chemical Society
图6 BPS诱导的肾脏和脾脏毒性[56,57]
Fig.6 BPS-induced nephrotoxicity and splenic injury[56,57]. Copyright 2018, American Chemical Society, and Copyright 2020, Elsevier, respectively
图7 孕期PM2.5暴露诱导子代行为障碍[75]
Fig.7 Gestational PM2.5exposure caused the behavior disorders in mouse offspring[75]. Copyright 2020, Elsevier
[1]
Dick S, Friend A, Dynes K, AlKandari F, Doust E, Cowie H, Ayres J G, Turner S W. BMJ Open, 2014, 4(11): e006554.

doi: 10.1136/bmjopen-2014-006554     URL     pmid: 25421340
[2]
Kabir E R, Rahman M S, Rahman I. Environ. Toxicol. Pharmacol., 2015, 40(1):241.

URL     pmid: 26164742
[3]
Kalkbrenner A E, Schmidt R J, Penlesky A C. Curr. Probl. Pediatr. Adolesc. Heal. Care, 2014, 44(10):277.
[4]
Kravchenko J, Corsini E, Williams M A, Decker W, Manjili M H, Otsuki T, Singh N, Al-Mulla F, Al-Temaimi R, Amedei A, Colacci A M, Vaccari M, Mondello C, Scovassi A I, Raju J, Hamid R A, Memeo L, Forte S, Roy R, Woodrick J, Salem H K, Ryan E P, Brown D G, Bisson W H, Lowe L, Lyerly H K. Carcinogenesis, 2015, 36(Suppl 1):S111.

doi: 10.1093/carcin/bgv033     URL    
[5]
Thompson P A, Khatami M, Baglole C J, Sun J, Harris S A, Moon E Y, Al-Mulla F, Al-Temaimi R, Brown D G, Colacci A M, Mondello C, Raju J, Ryan E P, Woodrick J, Scovassi A I, Singh N, Vaccari M, Roy R, Forte S, Memeo L, Salem H K, Amedei A, Hamid R A, Lowe L, Guarnieri T, Bisson W H. Carcinogenesis, 2015, 36(Suppl 1):S232.

doi: 10.1093/carcin/bgv038     URL    
[6]
Zeliger H I. Interdiscip. Toxicol., 2013, 6(3):103.

doi: 10.2478/intox-2013-0018     URL     pmid: 24678247
[7]
Multigner L, Ndong J R, Giusti A, Romana M, Delacroix-Maillard H, Cordier S, JÉgou B, Thome J P, Blanchet P. J. Clin. Oncol., 2010, 28(21):3457.

doi: 10.1200/JCO.2009.27.2153     URL     pmid: 20566993
[8]
Zhao C, Tang Z, Yan J C, Fang J, Wang H L, Cai Z W. Sci. Total. Environ., 2017, 592:357.

doi: 10.1016/j.scitotenv.2017.03.035     URL     pmid: 28319722
[9]
Caprioli R M, Farmer T B, Gile J. Anal. Chem., 1997, 69(23):4751.

doi: 10.1021/ac970888i     URL     pmid: 9406525
[10]
Zhao C, Cai Z W. Mass Spectrom. Rev., 2020,DOI: 10.1002/mas.21674.
[11]
Liu X, Hummon A B. Anal. Chem., 2015, 87(19):9508.

doi: 10.1021/acs.analchem.5b00419     URL     pmid: 26084404
[12]
Carletti E, Motta A, Migliaresi C. 3 D Cell Culture: Methods and Protocols, Methods in Molecular Biology, 2011, 695:17.

doi: 10.1007/978-1-60761-984-0_2     URL     pmid: 21042963
[13]
Huh D, Hamilton G A, Ingber D E. Trends Cell Biol., 2011, 21(12):745. 0bb0e88c-5fae-4353-bfff-0335823c824d

doi: 10.1016/j.tcb.2011.09.005     URL    
[14]
Pampaloni F, Reynaud E G, Stelzer E H K. Nat. Rev. Mol. Cell Biol., 2007, 8(10):839.

doi: 10.1038/nrm2236     URL     pmid: 17684528
[15]
Liu X, Weaver E M, Hummon A B. Anal. Chem., 2013, 85(13):6295.

doi: 10.1021/ac400519c     URL     pmid: 23724927
[16]
Jenkins S, Wang J, Eltoum I, Desmond R, Lamartiniere C A. Environ. Heal. Perspect., 2011, 119(11):1604.

doi: 10.1289/ehp.1103850     URL    
[17]
Marusyk A, Almendro V, Polyak K. Nat. Rev. Cancer, 2012, 12(5):323.

URL     pmid: 22513401
[18]
Dagogo-Jack I, Shaw A T. Nat. Rev. Clin. Oncol., 2018, 15(2):81.

doi: 10.1038/nrclinonc.2017.166     URL     pmid: 29115304
[19]
Junttila M R, de Sauvage F J. Nature, 2013, 501(7467):346.

URL     pmid: 24048067
[20]
Dairkee S H, Seok J, Champion S, Sayeed A, Mindrinos M, Xiao W Z, Davis R W, Goodson W H. Cancer Res., 2008, 68(7):2076.

URL     pmid: 18381411
[21]
Rochester J R, Bolden A L. Environ. Heal. Perspect., 2015, 123(7):643.
[22]
Rayner J L, Enoch R R, Fenton S E. Toxicol. Sci., 2005, 87(1):255.
[23]
Rudel R A, Fenton S E, Ackerman J M, Euling S Y, Makris S L. Environ. Heal. Perspect., 2011, 119(8):1053.
[24]
Fenton S E. Endocrinology, 2006, 147(6):s18.
[25]
Enoch R R, Stanko J P, Greiner S N, Youngblood G L, Rayner J L, Fenton S E. Environ. Heal. Perspect., 2007, 115(4):541.
[26]
Casadonte R, Caprioli R M. Nat. Protoc., 2011, 6(11):1695.

URL     pmid: 22011652
[27]
Ly A, Buck A, Balluff B, Sun N, Gorzolka K, Feuchtinger A, Janssen K P, Kuppen P J K, van de Velde C J H, Weirich G, Erlmeier F, Langer R, Aubele M, Zitzelsberger H, McDonnell L, Aichler M, Walch A. Nat. Protoc., 2016, 11(8):1428.

URL     pmid: 27414759
[28]
Wang T T, Cheng X L, Xu H X, Meng Y F, Yin Z B, Li X P, Hang W. Anal. Chem., 2020, 92(1):543.

URL     pmid: 31755699
[29]
Wang H A O, Grolimund D, Giesen C, Borca C N, Shaw-Stewart J R H, Bodenmiller B, Günther D. Anal. Chem., 2013, 85(21):10107.

URL     pmid: 23957530
[30]
Giesen C, Wang H A O, Schapiro D, Zivanovic N, Jacobs A, Hattendorf B, Schüffler P J, Grolimund D, Buhmann J M, Brandt S, Varga Z, Wild P J, Günther D, Bodenmiller B. Nat. Methods, 2014, 11(4):417.

URL     pmid: 24584193
[31]
Wang J, Wang Z Y, Liu F, Cai L S, Pan J B, Li Z P, Zhang S C, Chen H Y, Zhang X R, Mo Y X. Anal. Chem., 2018, 90(16):10009.

URL     pmid: 30028942
[32]
He J M, Sun C L, Li T G, Luo Z G, Huang L J, Song X W, Li X, Abliz Z. Adv. Sci., 2018, 5(11):1800250.
[33]
He J M, Huang L J, Tian R T, Li T G, Sun C L, Song X W, Lv Y, Luo Z G, Li X, Abliz Z. Anal. Chimica Acta, 2018, 1015:50.
[34]
Sun C L, Li T G, Song X W, Huang L J, Zang Q C, Xu J, Bi N, Jiao G G, Hao Y Z, Chen Y H, Zhang R P, Luo Z G, Li X, Wang L H, Wang Z H, Song Y M, He J M, Abliz Z. PNAS, 2019, 116(1):52.
[35]
Verbeeck N, Caprioli R M, van de Plas R. Mass Spectrom. Rev., 2020, 39(3):245.
[36]
Song X W, He J M, Pang X C, Zhang J, Sun C L, Huang L J, Li C, Zang Q C, Li X, Luo Z G, Zhang R P, Xie P, Liu X Y, Li Y, Chen X G, Abliz Z. Anal. Chem., 2019, 91(4):2838.

URL     pmid: 30636407
[37]
van de Plas R, Yang J H, Spraggins J, Caprioli R M. Nat. Methods, 2015, 12(4):366.
[38]
Zhao C, Tang Z, Xie P S, Lin K L, Chung A C K, Cai Z W. Environ. Sci. Technol., 2019, 53(19):11420.

URL     pmid: 31453682
[39]
Murray T, Maffini M, Ucci A, Sonnenschein C, Soto A. Reproductive Toxicol., 2007, 23(3):383.
[40]
Liao C Y, Liu F, Guo Y, Moon H B, Nakata H, Wu Q, Kannan K. Environ. Sci. Technol., 2012, 46(16):9138.

URL     pmid: 22784190
[41]
Chen D, Kannan K, Tan H L, Zheng Z G, Feng Y L, Wu Y, Widelka M. Environ. Sci. Technol., 2016, 50(11):5438.

URL     pmid: 27143250
[42]
Maffini M V, Rubin B S, Sonnenschein C, Soto A M. Mol. Cell. Endocrinol., 2006, 254/255:179.
[43]
Rezg R, El-Fazaa S, Gharbi N, Mornagui B. Environ. Int., 2014, 64:83.

URL     pmid: 24382480
[44]
Gowder S J T. Curr. Mol. Pharmacol., 2013, 6(3):163.

URL     pmid: 24720537
[45]
Boucher J G, Ahmed S, Atlas E. Endocrinology, 2016, 157(4):1397.
[46]
Boucher J G, GagnÉ R, Rowan-Carroll A, Boudreau A, Yauk C L, Atlas E. PLoS One, 2016, 11(9):e0163318.

URL     pmid: 27685785
[47]
Hessel E V S, Ezendam J, van Broekhuizen F A, Hakkert B, DeWitt J, Granum B, Guzylack L, Lawrence B P, Penninks A, Rooney A A, Piersma A H, van Loveren H. Reproductive Toxicol., 2016, 65:448.
[48]
Robinson L, Miller R. Curr. Environ. Heal. Rep., 2015, 2(4):379.
[49]
Yoshino S, Yamaki K, Li X J, Sai T, Yanagisawa R, Takano H, Taneda S, Hayashi H, Mori Y. Immunology, 2004, 112(3):489.

URL     pmid: 15196218
[50]
Midoro-Horiuti T, Tiwari R, Watson C S, Goldblum R M. Environ. Heal. Perspect., 2010, 118(2):273.
[51]
Mebius R E, Kraal G. Nat. Rev. Immunol., 2005, 5(8):606.

URL     pmid: 16056254
[52]
Dong Y D, Zhai L L, Zhang L, Jia L H, Wang X F. Mol. Cell. Toxicol., 2013, 9(4):401.
[53]
Gear R B, Belcher S M. Sci. Rep., 2017, 7:856.

URL     pmid: 28404993
[54]
Fu S N, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X H, Watkins S M, Ivanov A R, Hotamisligil G S. Nature, 2011, 473(7348):528.
[55]
Hatzivassiliou G, Zhao F P, Bauer D E, Andreadis C, Shaw A N, Dhanak D, Hingorani S R, Tuveson D A, Thompson C B. Cancer Cell, 2005, 8(4):311.

URL     pmid: 16226706
[56]
Albert C M, Campos H, Stampfer M J, Ridker P M, Manson J E, Willett W C, Ma J. N. Engl. J. Med., 2002, 346(15):1113.

URL     pmid: 11948270
[57]
van Meer G, Voelker D R, Feigenson G W. Nat. Rev. Mol. Cell Biol., 2008, 9(2):112.

URL     pmid: 18216768
[58]
Liu H H, Li W, He Q, Xue J J, Wang J Y, Xiong C Q, Pu X P, Nie Z X. Sci. Rep., 2017, 7:41954.

URL     pmid: 28157191
[59]
Rao S, Walters K B, Wilson L, Chen B, Bolisetty S, Graves D, Barnes S, Agarwal A, Kabarowski J H. Am. J. Physiol. -Ren. Physiol., 2016, 310(10):F1136.
[60]
Zhao C, Xie P S, Yong T, Wang H L, Chung A C K, Cai Z W. Anal. Chem., 2018, 90(5):3196.

URL     pmid: 29430921
[61]
Zhao C, Yong T, Zhang Y B, Jin Y F, Xiao Y, Wang H L, Zhao B, Cai Z W. Environ. Int., 2020, 135:105378.

URL     pmid: 31838264
[62]
Cho C C, Hsieh W Y, Tsai C H, Chen C Y, Chang H F, Lin C S. Int. J. Environ. Res. Public Heal., 2018, 15(7):1380.
[63]
Dagher Z, Garçon G, Billet S, Gosset P, Ledoux F, Courcot D, Aboukais A, Shirali P. Toxicology, 2006, 225(1):12.

URL     pmid: 16787692
[64]
Haberzettl P, Lee J, Duggineni D, McCracken J, Bolanowski D, O’Toole T E, Bhatnagar A, Conklin D J. Environ. Heal. Perspect., 2012, 120(6):848.
[65]
Lelieveld J, Evans J S, Fnais M, Giannadaki D, Pozzer A. Nature, 2015, 525(7569):367.

URL     pmid: 26381985
[66]
Lim Y H, Kim H, Kim J H, Bae S, Park H Y, Hong Y C. Environ. Heal. Perspect., 2012, 120(7):1023.
[67]
BovÉ H, Bongaerts E, Slenders E, Bijnens E M, Saenen N D, Gyselaers W, van Eyken P, Plusquin M, Roeffaers M B J, Ameloot M, Nawrot T S. Nat. Commun., 2019, 10:3866.
[68]
Levesque S, Taetzsch T, Lull M E, Kodavanti U, Stadler K, Wagner A, Johnson J A, Duke L, Kodavanti P, Surace M J, Block M L. Environ. Heal. Perspect., 2011, 119(8):1149.
[69]
RoquÉ P J, Dao K, Costa L G. NeuroToxicology, 2016, 56:204.
[70]
Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. Inhal. Toxicol., 2004, 16(6/7):437.
[71]
Block M L, CalderÓn-Garcidueñas L. Trends Neurosci., 2009, 32(9):506.
[72]
Woodward N, Finch C E, Morgan T E. AIMS Environ. Sci., 2015, 2(2):353.

URL     pmid: 27099868
[73]
Zhang T L, Zheng X R, Wang X, Zhao H, Wang T T, Zhang H X, Li W W, Shen H, Yu L. Int. J. Mol. Sci., 2018, 19(1):257.
[74]
Xiao G G, Wang M Y, Li N, Loo J A, Nel A E. J. Biol. Chem., 2003, 278(50):50781.

URL     pmid: 14522998
[75]
Zhao C, Xie P S, Yong T, Huang W, Liu J J, Wu D S, Ji F F, Li M, Zhang D D, Li R J, Dong C, Ma J, Dong Z, Liu S J, Cai Z W. Sci. Bull., 2021, 66:578.
[76]
Lagarrigue M, Lavigne R, Tabet E, Genet V, ThomÉ J P, Rondel K, GuÉvel B, Multigner L, Samson M, Pineau C. Anal. Chem., 2014, 86(12):5775.

URL     pmid: 24837422
[77]
Anderson D M G, Carolan V A, Crosland S, Sharples K R, Clench M R. Rapid Commun. Mass Spectrom., 2009, 23(9):1321.

URL     pmid: 19337978
[78]
Anderson D M G, Carolan V A, Crosland S, Sharples K R, Clench M R. Rapid Commun. Mass Spectrom., 2010, 24(22):3309.

URL     pmid: 20973006
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