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文化和建立具有高尿酸的自我更新人类肝脏 3D 类器官,用于筛选抗高尿酸血症功能化合物。

Culture and establishment of self-renewing human liver 3D organoids with high uric acid for screening antihyperuricemic functional compounds.

机构信息

School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.

The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou 510182, China.

出版信息

Food Chem. 2022 Apr 16;374:131634. doi: 10.1016/j.foodchem.2021.131634. Epub 2021 Nov 19.

DOI:10.1016/j.foodchem.2021.131634
PMID:34838408
Abstract

Hyperuricemia (HUA) is a metabolic disease caused by disorders of purine metabolism, the prevalence of which has increased worldwide. At present, most drugs aimed at lowering uric acid have toxic side effects, and in vitro screening of uric acid-lowering active substances are inefficient. Here, a long-term 3D human liver organoid culture system with high uric acid for screening and evaluating the efficacy of uric acid-lowering functional compounds. This liver organoids can be established from single hepatocytes and grown for multiple months, while retaining key morphological and functional features. Furthermore, establishment of HUA organoids model was verified by antihyperuricemic drugs allopurinol, as well as reported bioactive peptides, which significantly reduced uric acid production in the liver organoids (p < 0.05). The results demonstrated that it has the potential to be used as a rapid and valid in vitro model to screen antihyperuricemic compounds that mimics in vivo cell growth patterns.

摘要

高尿酸血症(HUA)是一种嘌呤代谢紊乱引起的代谢性疾病,其患病率在全球范围内呈上升趋势。目前,大多数降低尿酸的药物都有有毒的副作用,而体外筛选降低尿酸的活性物质效率低下。在这里,我们建立了一个长期的、具有高尿酸的 3D 人肝类器官培养系统,用于筛选和评估降低尿酸功能化合物的功效。这种肝类器官可以由单个肝细胞建立,并生长多个月,同时保留关键的形态和功能特征。此外,通过抗高尿酸血症药物别嘌醇以及报道的生物活性肽来验证 HUA 类器官模型,这些药物能显著降低肝类器官中的尿酸生成(p<0.05)。结果表明,它有可能成为一种快速有效的体外模型,用于筛选模拟体内细胞生长模式的抗高尿酸血症化合物。

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