ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2018, Vol. 27 ›› Issue (1): 69-73.DOI: 10.3969/j.issn.1006-298X.2018.01.016

• 论文 • 上一篇    下一篇

代谢组学在肾毒性药物评价中的应用

  

  • 出版日期:2018-02-28 发布日期:2018-03-01

Application of metabolomics in the evaluation of druginduced nephrotoxicity

  • Online:2018-02-28 Published:2018-03-01

摘要:

肾毒性评价是药物研发和市场应用的试金石,也是关系到人体健康状况与疾病转归的重要方面。其中,药物肾毒性的早期诊断是临床干预的难点。传统药物肾毒性评价通常以病理学诊断为基础,结合临床信息、生化指标进行综合判断。然而,上述方式不能满足灵敏、准确、无创的诊断需求,在临床应用中往往表现出延迟性与高度异质性。随着计算机技术和分子计量学的发展,代谢组学技术以其快速、灵敏、可定量、系统性的特点,在药物肾毒性评价领域展现出广阔的应用前景。历经十余年发展,基于模式动物模型的基础代谢组学研究成果显著,而实现前期研究成果的临床应用转化,尚且需要大样本、多中心研究证实。此外,由于试验设计、检测方法、数据处理方式的不同,现有研究结论差异明显。为克服上述研究瓶颈,需要整合不同类别肾毒性药物的代谢组学研究现状,并对关键代谢通路的改变进行重点分析。有效提取疾病状态下的代谢信息是将基础研究成果应用于临床的必要前提。于是,本文对代谢组学技术辅助药物肾毒性生物标志物筛选以及相关代谢通路指征的研究现状进行总结,以期为早日实现其临床辅助诊断提供参考。

关键词: 代谢组学, 药物, 肾毒性

Abstract:

With the development of computer technology and molecular metrology, metabolomics technology has become a wide applicable tool in the field of drug nephrotoxicity due to its rapid, sensitive, quantifiable and systematic characteristics. After more than ten years development, basic metabolomics researches based on the animal model achieve remarkable success, while there is still a need for large sample, multicenter studies for clinical transformation. In addition, due to different study designs, testing methods and data processing progresses, the obtained conclusions are all too often incoherent. In order to overcome the above research bottleneck, it is imperative to integrate the metabolomics researches of different types of nephrotoxic drugs and key metabolic pathways involved in drug toxicity. Effective extraction of metabolic information in the disease state is a prerequisite for applying the basic research results to clinical practice. This study summarizes the status quo of biomedical biomarkers screening and related metabolic pathways at drug nephrotoxicity in order to provide a reference for early clinical intervention.

Key words: metabolomics, drug, nephrotoxicity