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肾毒性评价体外替代模型研究进展

池慧钦 黎姿茵 王延 徐飞飞 何志妮 杨杏芬

池慧钦, 黎姿茵, 王延, 徐飞飞, 何志妮, 杨杏芬. 肾毒性评价体外替代模型研究进展[J]. 中国公共卫生, 2021, 37(6): 1035-1040. doi: 10.11847/zgggws1126789
引用本文: 池慧钦, 黎姿茵, 王延, 徐飞飞, 何志妮, 杨杏芬. 肾毒性评价体外替代模型研究进展[J]. 中国公共卫生, 2021, 37(6): 1035-1040. doi: 10.11847/zgggws1126789
CHI Hui-qin, LI Zi-yin, WANG Yan, . Progress in researches on in vitro alternative model for nephrotoxicity evaluation[J]. Chinese Journal of Public Health, 2021, 37(6): 1035-1040. doi: 10.11847/zgggws1126789
Citation: CHI Hui-qin, LI Zi-yin, WANG Yan, . Progress in researches on in vitro alternative model for nephrotoxicity evaluation[J]. Chinese Journal of Public Health, 2021, 37(6): 1035-1040. doi: 10.11847/zgggws1126789

肾毒性评价体外替代模型研究进展

doi: 10.11847/zgggws1126789
基金项目: 国家重点研发计划(2018YFC1603101);广东省重点研发计划(2019B020210002)
详细信息
    作者简介:

    池慧钦(1994 – ),女,福建闽清人,硕士在读,研究方向:食品毒理学与替代毒理学

    通信作者:

    杨杏芬,E-mail:xfyang@vip.163.com

  • 中图分类号: R 99

Progress in researches on in vitro alternative model for nephrotoxicity evaluation

  • 摘要: 随着《21世纪毒性测试:愿景与策略》的提出,毒性测试的重点开始从整体动物实验转向基于人类细胞或细胞组分等替代方法的测试策略。由于肾毒性物质的靶器官选择性,且药物诱导的肾损伤是新药开发时需解决的重要问题,故需良好的体外替代模型来评价包括药物在内的外源性化合物的肾脏毒性。然而,现有的体外模型由于缺少肾小管上皮细胞在体内的形态及功能,难以预测外源性化合物的肾脏毒性。肾体外替代模型的细胞来源、特点、培养条件以及检测终点是在建立体外替代模型时重点考虑的问题。多功能干细胞诱导分化肾细胞的出现、3D培养及肾脏芯片技术的发展、组学技术、高内涵筛选的应用为体外模型的建立及模型预测结果从体外到体内的外推提供了新思路。
  • 表  1  与急性肾损伤相关的体内及体外生物标志物

    生物标志物标志性损伤部位特异性参考文献
    FDA及EMA认证的生物标志物
    肾损伤因子 毒性、缺血引起AKI/早期急性肾小管损伤 近端小管 [3234]
    丛生蛋白 毒性、缺血引起AKI、单侧输尿管梗阻 近端小管及远端小管 [3233]
    三叶因子 – 3 与肾组织病理学损伤相关 近端小管 [3233]
    β2微球蛋白 毒性、缺血引起AKI、肾脏移植 肾小球及近端小管 [32]
    血清半胱氨酸蛋白酶抑制剂C 肾小球滤过功能、毒性、缺血引起AKI 肾小球及近端小管 [3233]
    尿总蛋白 慢性肾损伤(CKD)、肾小球滤过功能或肾小管重吸收功能受损 肾小球及肾小管 [32]
    白蛋白 毒性、缺血引起AKI 肾小球及近端小管 [3233]
    肾乳头抗原 – 1 集合管损伤 集合管 [32]
    其他肾脏相关生物标志物
    γ – 谷氨酰转肽酶 肾小管上皮刷状缘受损 肾小管上皮刷状缘 [35]
    N – 乙酰 – β – D – 葡萄糖苷酶 毒性、缺血引起AKI、肾脏移植、慢性肾小球疾病 近端小管溶酶体 [36]
    骨桥蛋白 毒性、缺血引起AKI、单侧输尿管梗阻 无部位特异性 [37]
    钙结合蛋白 远端小管及集合管功能 无部位特异性 [3738]
    基质金属蛋白酶抑制剂 – 1 肾间质纤维化 无部位特异性 [38]
    中性粒细胞明胶酶相关载脂蛋白 毒性、缺血引起AKI/与炎症相关 近端小管及远端小管 [3839]
    白介素 – 18 炎症反应/毒性、缺血引起AKI 近端小管 [21]
    白介素 – 6 炎症反应 能够在近端小管细胞中表达 [18, 21]
    白介素 – 8 炎症反应 能够在近端小管细胞中表达 [18, 21]
    血红素加氧酶 – 1 氧化应激、炎症反应 近端小管、远端小管、集合管及髓袢上皮细胞 [17]
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  • 接收日期:  2019-11-04
  • 网络出版日期:  2020-06-24
  • 刊出日期:  2021-06-03

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