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3D类器官模型的研究进展及其在化学品毒理学评价中的应用展望

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刘薇, 梅玺丽, 陈雨萌, 向哲源, 高泽欣, 邢立国, 赵慧敏, 刘猛, 陈景文. 3D类器官模型的研究进展及其在化学品毒理学评价中的应用展望[J]. 生态毒理学报, 2021, 16(4): 32-42. doi: 10.7524/AJE.1673-5897.20200817001
引用本文: 刘薇, 梅玺丽, 陈雨萌, 向哲源, 高泽欣, 邢立国, 赵慧敏, 刘猛, 陈景文. 3D类器官模型的研究进展及其在化学品毒理学评价中的应用展望[J]. 生态毒理学报, 2021, 16(4): 32-42. doi: 10.7524/AJE.1673-5897.20200817001
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Liu Wei, Mei Xili, Chen Yumeng, Xiang Zheyuan, Gao Zexin, Xing Liguo, Zhao Huimin, Liu Meng, Chen Jingwen. Progress in 3D Organoid Models and Application Perspectives in Toxicity Test of Chemicals[J]. Asian Journal of Ecotoxicology, 2021, 16(4): 32-42. doi: 10.7524/AJE.1673-5897.20200817001
Citation: Liu Wei, Mei Xili, Chen Yumeng, Xiang Zheyuan, Gao Zexin, Xing Liguo, Zhao Huimin, Liu Meng, Chen Jingwen. Progress in 3D Organoid Models and Application Perspectives in Toxicity Test of Chemicals[J]. Asian Journal of Ecotoxicology, 2021, 16(4): 32-42. doi: 10.7524/AJE.1673-5897.20200817001
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3D类器官模型的研究进展及其在化学品毒理学评价中的应用展望

  • 1. 大连理工大学环境学院, 工业生态与环境工程重点实验室, 大连 116024;

  • 2. 中化集团沈阳化工研究院有限公司, 沈阳 110027

    • 作者简介: 刘薇(1980-),女,博士,教授,研究方向为持久性有机污染物毒性效应和机理以及干细胞毒理学模型原理和应用,E-mail:liu_wei@dlut.edu.cn
    通讯作者: 刘薇, E-mail: liu_wei@dlut.edu.cn ; 
  • 基金项目:

    国家重点研发计划项目（2018YFE0110700）；国家自然科学基金资助项目（21661142001，21777020）；中央高校基本科研业务费（DUT20LAB102，DUT20LK19）

  • 中图分类号: X171.5

Progress in 3D Organoid Models and Application Perspectives in Toxicity Test of Chemicals

  • 1. Key Laboratory of Industrial Ecology and Environmental Engineering of Ministry of Education, School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China;

  • 2. Shenyang Research Institute of Chemical Industry of SINOCHEM Group, Shenyang 110027, China

    • Corresponding author: Liu Wei, liu_wei@dlut.edu.cn ; 
  • Fund Project:

  • 摘要: 化学品毒理学评价主要采用2D细胞培养体系和动物实验模型，但2种模型均存在一定的局限性。2D细胞培养常用特定细胞系，与体内多细胞组织及其生理功能差异较大。动物实验耗时、昂贵，并受伦理学限制，且存在种属差异问题。3D类器官模型可模拟组织器官的复杂结构和功能，产生细胞间和细胞-基质相互作用，与体内生理反应更为相似，因此能更准确地反映毒性效应和机理。类器官模型在化学品毒理学评价领域具有良好的应用前景，将显著提升毒理学基础研究能力以及对化学品风险评价和管理的支撑作用，但相关研究尚处于起步阶段。本文从类器官的生理学特性、构建方法及组织类型等方面，重点讨论了类器官模型在化学品毒理学研究中的适用性，并提出了存在的挑战和对策。
    Abstract: Toxicity assessment of chemicals predominantly adopted either 2D cell culture or animal models whereas both models have intrinsic flaws. 2D cell culture systems are usually derived from a specific set of cell lines, differing from the tissue function encountered in vivo containing multiple cell types. Animal models are limited by the cost and time, associated ethical concerns and xenogeneity. 3D organoids achieve a greater level of structural and functional complexity more closely analogous to in vivo physiology, showing cell-cell and cell-extracellular matrix interactions, and thus enabling a more accurate reflection of the toxic effects and mechanisms. With promising perspectives, the progresses in organoid toxicology would significantly promote the fundamental toxicology research, and support the chemicals risk assessment and regulation as well. However, organoid-based toxicological research of chemicals is still in its infancy. In this review, we discussed recent developments and trends in organoid model concerning the physiological features, development systems and methods, and tissue-specific types, focusing on its feasibility in toxicological researches of chemicals, and the challenges and strategies are also proposed.
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  • 孙广权, 杨慧妮, 刘小春, 等. 我国PM2.5主要组分及健康危害特征研究进展[J]. 环保科技, 2015, 21(1):54-59

    Sun G Q, Yang H N, Liu X C, et al. PM2.5 in China:Chemical compositions and health effects[J]. Environmental Protection and Technology, 2015, 21(1):54-59(in Chinese)

    Dicker D, Nguyen G, Abate D, et al. Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017:A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2018, 392(10159):1684-1735
    李继忠, 边毓尧, 郭文有, 等. PM2.5与呼吸系统疾病发病率关系流行病学调查研究[J]. 陕西医学杂志, 2018, 47(6):805-808

    Li J Z, Bian Y Y, Guo W Y, et al. Epidemiological survey on the incidence of respiratory diseases in high PM2.5 area[J]. Shaanxi Medical Journal, 2018, 47(6):805-808(in Chinese)

    高丽云, 聂林坤, 李潇, 等. 大气细颗粒物PM2.5对心血管疾病损害机制的研究进展[J]. 新乡医学院学报, 2018, 35(7):551-553
    Woodward N C, Pakbin P, Saffari A, et al. Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons[J]. Neurobiology of Aging, 2017, 53:48-58
    Ibironke O, Carranza C, Sarkar S, et al. Urban air pollution particulates suppress human T-cell responses toMycobacterium tuberculosis [J]. International Journal of Environmental Research and Public Health, 2019, 16(21):4112
    胡富宇, 郭婷婷, 朱珊珊, 等. 台州市大气PM2.5对成年男性精液质量的影响[J]. 预防医学, 2019, 31(1):20-22

    , 27 Hu F Y, Guo T T, Zhu S S, et al. Atmospheric PM2.5 exposure on semen quality in adult men in Taizhou[J]. Preventive Medicine, 2019, 31(1):20-22, 27(in Chinese)

    Guan Q Q, Chen S Y, Wang B Q, et al. Effects of particulate matter exposure on semen quality:A retrospective cohort study[J]. Ecotoxicology and Environmental Safety, 2020, 193:110319
    Santi D, Magnani E, Michelangeli M, et al. Seasonal variation of semen parameters correlates with environmental temperature and air pollution:A big data analysis over 6 years[J]. Environmental Pollution, 2018, 235:806-813
    Lao X Q, Zhang Z L, Lau A K H, et al. Exposure to ambient fine particulate matter and semen quality in Taiwan[J]. Occupational and Environmental Medicine, 2018, 75(2):148-154
    吴黎, 张海, 彭哲, 等. 大气细颗粒物长期暴露对男性精子质量的影响[J]. 公共卫生与预防医学, 2018, 29(6):13-16

    Wu L, Zhang H, Peng Z, et al. Association between long-term exposure to ambient fine particulate matter and semen quality[J]. Journal of Public Health and Preventive Medicine, 2018, 29(6):13-16(in Chinese)

    Radwan M, Dziewirska E, Radwan P, et al. Air pollution and human sperm sex ratio[J]. American Journal of Men's Health, 2018, 12(4):907-912
    Huang X J, Zhang B, Wu L, et al. Association of exposure to ambient fine particulate matter constituents with semen quality among men attending a fertility center in China[J]. Environmental Science & Technology, 2019, 53(10):5957-5965
    Zhou N Y, Jiang C T, Chen Q, et al. Exposures to atmospheric PM10 and PM10-2.5 affect male semen quality:Results of MARHCS study[J]. Environmental Science & Technology, 2018, 52(3):1571-1581
    Yang S P, Tan Y F, Mei H, et al. Ambient air pollution the risk of stillbirth:A prospective birth cohort study in Wuhan, China[J]. International Journal of Hygiene and Environmental Health, 2018, 221(3):502-509
    Green R, Sarovar V, Malig B, et al. Association of stillbirth with ambient air pollution in a California cohort study[J]. American Journal of Epidemiology, 2015, 181(11):874-882
    Arroyo V, Díaz J, Carmona R, et al. Impact of air pollution and temperature on adverse birth outcomes:Madrid, 2001-2009[J]. Environmental Pollution, 2016, 218:1154-1161
    Liu X, Ye Y F, Chen Y, et al. Effects of prenatal exposure to air particulate matter on the risk of preterm birth and roles of maternal and cord blood LINE-1 methylation:A birth cohort study in Guangzhou, China[J]. Environment International, 2019, 133(Pt A):105177
    Stieb D M, Chen L, Beckerman B S, et al. Associations of pregnancy outcomes and PM2.5 in a national Canadian study[J]. Environmental Health Perspectives, 2016, 124(2):243-249
    Melody S M, Ford J, Wills K, et al. Maternal exposure to fine particulate matter from a coal mine fire and birth outcomes inVictoria, Australia[J]. Environment International, 2019, 127:233-242
    Liang Z J, Yang Y, Qian Z M, et al. Ambient PM2.5 and birth outcomes:Estimating the association and attributable risk using a birth cohort study in nine Chinese cities[J]. Environment International, 2019, 126:329-335
    Dadvand P, Rankin J, Rushton S, et al. Ambient air pollution and congenital heart disease:A register-based study[J]. Environmental Research, 2011, 111(3):435-441
    Agay-Shay K, Friger M, Linn S, et al. Air pollution and congenital heart defects[J]. Environmental Research, 2013, 124:28-34
    Saenen N D, Plusquin M, Bijnens E, et al. In utero fine particle air pollution and placental expression of genes in the brain-derived neurotrophic factor signaling pathway:An ENVIRONAGE birth cohort study[J]. Environmental Health Perspectives, 2015, 123(8):834-840
    潘晓, 邓美洲, 刘琳, 等. 大气PM2.5对人卵巢颗粒细胞的毒性作用及氧化损伤研究[J]. 环境与健康杂志, 2018, 35(3):206-209

    Pan X, Deng M Z, Liu L, et al. Atmospheric PM2.5-induced toxicity and oxidative damage to human ovarian granulosa cells[J]. Journal of Environment and Health, 2018, 35(3):206-209(in Chinese)

    Clemens T, Turner S, Dibben C. Maternal exposure to ambient air pollution and fetal growth in North-East Scotland:A population-based study using routine ultrasound scans[J]. Environment International, 2017, 107:216-226
    Zang H Y, Cheng H, Song W Y, et al. Ambient air pollution and the risk of stillbirth:A population-based prospective birth cohort study in the coastal area of China[J]. Environmental Science and Pollution Research International, 2019, 26(7):6717-6724
    Li S S, Wang H Y, Hu H T, et al. Effect of ambient air pollution on premature SGA in Changzhou City, 2013-2016:A retrospective study[J]. BMC Public Health, 2019, 19(1):705
    Zhu J M, Lee R W, Twum C, et al. Exposure to ambient PM2.5 during pregnancy and preterm birth in metropolitan areas of the state of Georgia[J]. Environmental Science and Pollution Research, 2019, 26(3):2492-2500
    Yorifuji T, Kashima S, Diez M H, et al. Prenatal exposure to outdoor air pollution and child behavioral problems at school age in Japan[J]. Environment International, 2017, 99:192-198
    周逢海, 周川, 吕海迪, 等. 细颗粒物对雄性小鼠生殖功能的影响[J]. 海南医学, 2019, 30(5):545-548

    Zhou F H, Zhou C, Lv H D, et al. Effect of fine particles on reproductive function of male mice[J]. Hainan Medical Journal, 2019, 30(5):545-548(in Chinese)

    Yang Y Y, Yang T T, Liu S X, et al. Concentrated ambient PM2.5 exposure affects mice sperm quality and testosterone biosynthesis[J]. PeerJ, 2019, 7:e8109
    Qiu L L, Chen M J, Wang X K, et al. Exposure to concentrated ambient PM2.5 compromises spermatogenesis in a mouse model:Role of suppression of hypothalamus-pituitary-gonads axis[J]. Toxicological Sciences, 2018, 162(1):318-326
    严超, 曹希宁, 沈炼桔, 等. 汽车尾气来源PM2.5颗粒物长期暴露导致SD雄鼠生殖功能损害[J]. 中华男科学杂志, 2016, 22(2):104-109

    Yan C, Cao X N, Shen L J, et al. Long-term exposure to PM2.5 from automobile exhaust results in reproductive dysfunction in male rats[J]. National Journal of Andrology, 2016, 22(2):104-109(in Chinese)

    Liao B Q, Liu C B, Xie S J, et al. Effects of fine particulate matter (PM2.5) on ovarian function and embryo quality in mice[J]. Environment International, 2020, 135:105338
    张丰泉, 董恩恒, 王茂, 等. PM2.5对雌鼠生殖内分泌水平和妊娠结局的影响[J]. 中国实验动物学报, 2017, 25(4):455-460

    Zhang F Q, Dong E H, Wang M, et al. Effects of PM2.5 on reproductive hormone levels and pregnancy outcome in female rats[J]. Acta Laboratorium Animalis Scientia Sinica, 2017, 25(4):455-460(in Chinese)

    张丰泉, 赵杉, 董恩恒, 等. 核转录因子NF-E2相关因子2信号通路在PM2.5致雌性大鼠生殖损伤中的作用[J]. 中国实验动物学报, 2018, 26(5):639-643

    Zhang F Q, Zhao S, Dong E H, et al. Effect of NF-E2 related factor 2 pathway activation on PM2.5 induced reproductive injury in female rats[J]. Acta Laboratorium Animalis Scientia Sinica, 2018, 26(5):639-643(in Chinese)

    张丰泉, 董恩恒, 薛玉雪. PM2.5短期暴露对大鼠子宫组织的损伤及其作用机制[J]. 中国实验动物学报, 2019, 27(6):740-746

    Zhang F Q, Dong E H, Xue Y X. Effect and mechanism of short-term exposure to PM2.5 on the rat uterine injury[J]. Acta Laboratorium Animalis Scientia Sinica, 2019, 27(6):740-746(in Chinese)

    李久存, 魏永杰, 陈田, 等. 妊娠期和哺乳期暴露于大气颗粒物对仔鼠中枢神经系统的影响[J]. 环境与健康杂志, 2011, 28(5):377-379

    Li J C, Wei Y J, Chen T, et al. Effects of maternal exposure to atmospheric particulates during pregnancy and lactation period on central nervous system of filial generation among rats[J]. Journal of Environment and Health, 2011, 28(5):377-379(in Chinese)

    Klocke C, Allen J L, Sobolewski M, et al. Neuropathological consequences of gestational exposure to concentrated ambient fine and ultrafine particles in the mouse[J]. Toxicological Sciences, 2017, 156(2):492-508
    Klocke C, Allen J L, Sobolewski M, et al. Exposure to fine and ultrafine particulate matter during gestation alters postnatal oligodendrocyte maturation, proliferation capacity, and myelination[J]. NeuroToxicology, 2018, 65:196-206
    王婷婷, 郑昕蕊, 李文燕, 等. 母源性PM2.5暴露致子代鼠大脑皮层神经炎症与星形胶质细胞和小胶质细胞激活[J]. 中国组织化学与细胞化学杂志, 2018, 27(4):313-320

    Wang T T, Zheng X R, Li W Y, et al. Maternal PM2.5 exposure induces the activation of astrocytes and microglia and subsequent neuroinflammation in the cerebral cortex in mouse offspring[J]. Chinese Journal of Histochemistry and Cytochemistry, 2018, 27(4):313-320(in Chinese)

    Ren L H, Huang J, Wei J L, et al. Maternal exposure to fine particle matters cause autophagy via UPR-mediated PI3K-mTOR pathway in testicular tissue of adult male mice in offspring[J]. Ecotoxicology and Environmental Safety, 2020, 189:109943
    郑昕蕊, 赵会, 田换兵, 等. 妊娠期PM2.5暴露影响子代鼠主要脏器发育[J]. 中国组织化学与细胞化学杂志, 2017, 26(4):366-372

    Zheng X R, Zhao H, Tian H B, et al. PM2.5 exposure during pregnancy causes abnormal development of major organs in offspring mice[J]. Chinese Journal of Histochemistry and Cytochemistry, 2017, 26(4):366-372(in Chinese)

    巩艳, 李文燕, 郑昕蕊, 等. 妊娠期大气细颗粒物暴露对新生小鼠肝脏发育的影响[J]. 中国组织化学与细胞化学杂志, 2016, 25(5):406-410

    Gong Y, Li W Y, Zheng X R, et al. Effects of gestational exposure to atmospheric fine particulate matter on liver development of newborn mice[J]. Chinese Journal of Histochemistry and Cytochemistry, 2016, 25(5):406-410(in Chinese)

    林彬彬. 大鼠妊娠前及妊娠期福州地区PM2.5暴露对子代肾发育及肾脏功能的远期影响[D]. 福州:福建医科大学, 2016:22-35 Lin B B. Prenatal and perinatal exposure to ambient PM2.5

    of Fuzhou on the renal development and long-term function[D]. Fuzhou:Fujian Medical University, 2016:22-35(in Chinese)

    汤雯婷, 匡丽云, 龚景进, 等. 母源性细颗粒物暴露对仔鼠生长发育及肺功能的影响[J]. 中华围产医学杂志, 2016, 19(2):108-113
    de Barros Mendes Lopes T, Groth E E, Veras M, et al. Pre-and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life[J]. Environmental Pollution, 2018, 241:511-520
    洪新如, 刘超斌, 黄惠娟, 等. 环境大气细颗粒物宫内暴露对大鼠子代免疫功能相关指标的影响[J]. 中华围产医学杂志, 2018, 21(2):94-101
    Rhee J, Han E, Nam K J, et al. Assessment of hair cell damage and developmental toxicity after fine particulate matter 2.5μm (PM2.5) exposure using zebrafish (Danio rerio) models[J]. International Journal of Pediatric Otorhinolaryngology, 2019, 126:109611
    吴德生, 王宏辉, 袁建辉, 等. 细颗粒物对斑马鱼胚胎发育的影响[J]. 癌变·畸变·突变, 2018, 30(4):307-309

    , 314 Wu D S, Wang H H, Yuan J H, et al. Effect of fine particle exposure on development of zebrafish embryos[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(4):307-309, 314(in Chinese)

    吴德生, 杨飞, 袁建辉, 等. PM2.5对斑马鱼胚胎发育早期氧化应激和DNA甲基化调控相关基因表达的影响[J]. 癌变·畸变·突变, 2017, 29(5):379-382

    Wu D S, Yang F, Yuan J H, et al. Effect of PM2.5 on expression of oxidative stress and DNA methylation genes during early development of zebrafish embryos[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(5):379-382(in Chinese)

    Zhang Y, Li S Y, Li J J, et al. Developmental toxicity induced by PM2.5 through endoplasmic reticulum stress and autophagy pathway in zebrafish embryos[J]. Chemosphere, 2018, 197:611-621
    王云彪, 侯晓丽, 武海涛, 等. PM2.5对秀丽隐杆线虫的毒性效应[J]. 城市环境与城市生态, 2012, 25(6):10-13

    Wang Y B, Hou X L, Wu H T, et al. Toxicological exposure effect test of usingC. elegans as a model organism[J]. Urban Environment snd Urban Ecology, 2012, 25(6):10-13(in Chinese)

    Sun L M, Lin Z Q, Liao K, et al. Adverse effects of coal combustion related fine particulate matter (PM2.5) on nematodeCaenorhabditis elegans [J]. Science of the Total Environment, 2015, 512-513:251-260
    Zhao Y L, Lin Z Q, Jia R H, et al. Transgenerational effects of traffic-related fine particulate matter (PM2.5) on nematodeCaenorhabditis elegans [J]. Journal of Hazardous Materials, 2014, 274:106-114
    Wang M D, Nie Y G, Liu Y, et al. Transgenerational effects of diesel particulate matter onCaenorhabditis elegans through maternal and multigenerational exposure[J]. Ecotoxicology and Environmental Safety, 2019, 170:635-643
    Ebisu K, Bell M L. Airborne PM2.5 chemical components and low birth weight in the northeastern and mid-Atlantic regions of the United States[J]. Environmental Health Perspectives, 2012, 120(12):1746-1752
    Sun X L, Luo X P, Zhao C M, et al. The associations between birth weight and exposure to fine particulate matter (PM2.5) and its chemical constituents during pregnancy:A meta-analysis[J]. Environmental Pollution, 2016, 211:38-47
    Bell M L, Belanger K, Ebisu K, et al. Prenatal exposure to fine particulate matter and birth weight[J]. Epidemiology, 2010, 21(6):884-891
    王芳, 李岩, 卢昕烁, 等. PM2.5对血管内皮细胞氧化应激和凋亡的影响及机制[J]. 中国病理生理杂志, 2017, 33(3):423-427

    Wang F, Li Y, Lu X S, et al. Oxidative stress and apoptosis in endothelial cells exposed to PM2.5[J]. Chinese Journal of Pathophysiology, 2017, 33(3):423-427(in Chinese)

    商学军, 叶章群, 熊承良, 等. 活性氧致人精子运动功能和存活力变化的分析[J]. 中华男科学, 2003, 9(6):439-442

    Shang X J, Ye Z Q, Xiong C L, et al. Analysis of the changes of movement function and viability in human spermatozoa induced by reactive oxygen species[J]. Acto Andrologica Sinica, 2003, 9(6):439-442(in Chinese)

    陈霞. 活性氧在卵泡发育及胚胎发育中的作用[J]. 实用医学杂志, 2008, 24(11):2014-2015
    de Melo J O, Soto S F, Katayama I A, et al. Inhalation of fine particulate matter during pregnancy increased IL-4 cytokine levels in the fetal portion of the placenta[J]. Toxicology Letters, 2015, 232(2):475-480
    Zhou L X, Su X, Li B H, et al. PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse[J]. Ecotoxicology and Environmental Safety, 2019, 169:551-563
    黄佳伟, 鲁娴娴, 崔海燕, 等. PM2.5通过NF-κB/NLRP3途径促进金黄色葡萄球菌肺炎的研究[J]. 生态毒理学报, 2019, 14(5):133-143

    Huang J W, Lu X X, Cui H Y, et al.Staphylococcus aureus pneumonia aggravation by PM2.5 via NF-κB/NLRP3 pathway[J]. Asian Journal of Ecotoxicology, 2019, 14(5):133-143(in Chinese)

    邹杨, 李淑珍, 李新鸣, 等. PM2.5通过ROS-Nrf2/NF-κB信号通路诱导人支气管上皮细胞炎症反应[J]. 中国公共卫生, 2020, 36(10):1438-1442

    Zou Y, Li S Z, Li X M, et al. PM2.5 induces inflammation in human bronchial epithelial cells through ROS-Nrf2 signaling pathway[J]. Chinese Journal of Public Health, 2020, 36(10):1438-1442(in Chinese)

    颜森波, 于国伟, 谌慧. PM2.5对DNA的损伤作用概述[J]. 职业与健康, 2015, 31(6):847-850

    Yan S B, Yu G W, Chen H. An overview on effect of PM2.5 on DNA damage[J]. Occupation and Health, 2015, 31(6):847-850(in Chinese)

    Arlt V M, Zhan L, Schmeiser H H, et al. DNA adducts and mutagenic specificity of the ubiquitous environmental pollutant 3-nitrobenzanthrone in Muta Mouse[J]. Environmental and Molecular Mutagenesis, 2004, 43(3):186-195
    Topinka J, Rossner P Jr, Milcova A Jr, et al. DNA adducts and oxidative DNA damage induced by organic extracts from PM2.5 in an acellular assay[J]. Toxicology Letters, 2011, 202(3):186-192
    张琳, 牛静萍, 徐佳, 等. 大气细颗粒物PM2.5对大鼠睾丸组织细胞周期的影响[J]. 生态毒理学报, 2009, 4(2):271-275

    Zhang L, Niu J P, Xu J, et al. Effects of PM2.5 on the cell cycle of testis spermatogenic cells in rats[J]. Asian Journal of Ecotoxicology, 2009, 4(2):271-275(in Chinese)

    Scull C M, Tabas I. Mechanisms of ER stress-induced apoptosis in atherosclerosis[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2011, 31(12):2792-2797
    Liu X N, Jin X T, Su R J, et al. The reproductive toxicology of male SD rats after PM2.5 exposure mediated by the stimulation of endoplasmic reticulum stress[J]. Chemosphere, 2017, 189:547-555
    Cao X N, Shen L J, Wu S D, et al. Urban fine particulate matter exposure causes male reproductive injury through destroying blood-testis barrier (BTB) integrity[J]. Toxicology Letters, 2017, 266:1-12
    Liu B, Shen L J, Zhao T X, et al. Automobile exhaust-derived PM2.5 induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in Sertoli cells of rats[J]. Ecotoxicology and Environmental Safety, 2020, 189:110053
    Liu J H, Ren L H, Wei J L, et al. Fine particle matter disrupts the blood-testis barrier by activating TGF-β3/p38 MAPK pathway and decreasing testosterone secretion in rat[J]. Environmental Toxicology, 2018, 33(7):711-719
    Oh S. Disturbance in testosterone production in leydig cells by polycyclic aromatic hydrocarbons[J]. Development & Reproduciton, 2014, 18(4):187-195
    O'Donnell L, McLachlan R I, Wreford N G, et al. Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium[J]. Biology of Reproduction, 1996, 55(4):895-901
    Ramaswamy S, Weinbauer G F. Endocrine control of spermatogenesis:Role of FSH and LH/testosterone[J]. Spermatogenesis, 2014, 4(2):e996025
    Corradi P F, Corradi R B, Greene L W. Physiology of the hypothalamic pituitary gonadal axis in the male[J]. The Urologic Clinics of North America, 2016, 43(2):151-162
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  • 收稿日期:  2020-08-17

3D类器官模型的研究进展及其在化学品毒理学评价中的应用展望

    通讯作者: 刘薇, E-mail: liu_wei@dlut.edu.cn ; 
    作者简介: 刘薇(1980-),女,博士,教授,研究方向为持久性有机污染物毒性效应和机理以及干细胞毒理学模型原理和应用,E-mail:liu_wei@dlut.edu.cn
  • 1. 大连理工大学环境学院, 工业生态与环境工程重点实验室, 大连 116024;
  • 2. 中化集团沈阳化工研究院有限公司, 沈阳 110027
  • 收稿日期:  2020-08-17
基金项目:

国家重点研发计划项目（2018YFE0110700）；国家自然科学基金资助项目（21661142001，21777020）；中央高校基本科研业务费（DUT20LAB102，DUT20LK19）

摘要: 化学品毒理学评价主要采用2D细胞培养体系和动物实验模型，但2种模型均存在一定的局限性。2D细胞培养常用特定细胞系，与体内多细胞组织及其生理功能差异较大。动物实验耗时、昂贵，并受伦理学限制，且存在种属差异问题。3D类器官模型可模拟组织器官的复杂结构和功能，产生细胞间和细胞-基质相互作用，与体内生理反应更为相似，因此能更准确地反映毒性效应和机理。类器官模型在化学品毒理学评价领域具有良好的应用前景，将显著提升毒理学基础研究能力以及对化学品风险评价和管理的支撑作用，但相关研究尚处于起步阶段。本文从类器官的生理学特性、构建方法及组织类型等方面，重点讨论了类器官模型在化学品毒理学研究中的适用性，并提出了存在的挑战和对策。

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