中国药理学与毒理学杂志2024，Vol.38Issue(4)：279-285,7.DOI:10.3867/j.issn.1000-3002.2024.04.005
基于人肾类器官构建顺铂诱导急性肾损伤模型
Modeling acute kidney injury induced by cisplatin in human kidney organoids
马瑞麟 1吴成君 1岳亮 2贠志敏 2楼张蓉 1刘琦 1崔宏图 1钟鹏飞 2高卓 3檀英霞2
作者信息
- 1. 大连理工大学生物医学工程学院,辽宁 大连 116024
- 2. 军事科学院军事医学研究院卫生勤务与血液研究所,北京 100850
- 3. 空军特色医学中心肾病科,北京 100089
- 折叠
摘要
Abstract
OBJECTIVE To establish a cisplatin induced acute kidney injury(AKI)model based on human kidney organoids.METHODS ①Kidney organoids containing various cell types were designed and constructed based on human induced pluripotent stem cells(hiPSC)induction techniques,and the tissue structure and cell types were identified by HE staining and immunofluorescence.② Based on the constructed human kidney organoid model,the broad-spectrum anticancer drug cisplatin was used as the experimental drug,and three concentration gradients of 20,50 and 75 μmol·L-1 were applied to the human kidney organoid model.The samples were collected 48 h later,and the cell viability was detected by observing the morphological changes of kidney organoids.The expression levels of renal injury factor-1(Kim-1)and inflammatory cytokine interleukin-8(IL-8)were detected with real-time quan-titative PCR to determine the degree and location of renal injury.RESULTS ①Histological and immu-nofluorescence results showed that mature human renal organoids could be produced after iPSC-induced differentiation.The organoids had primitive tubular structure and included various cell types including the proximal tubular tubular,distal tubular tubular,podocytes,interstitial endothelial cells and tubular epithelial cells.② Single administration of three concentrations of cisplatin resulted in the destruction of cell morphology and structure,and a large number of tubular structures disappeared.Live/Dead staining showed that renal organoids exhibited dose-dependent apoptosis to cisplatin.With cisplatin at the concentration of 20 μmol·L-1,cell viability fell below 50%,and approached 0 at a maxi-mum concentration of 75 μmol·L-1.③Kim-1 and IL-8 were significantly increased at different concentra-tions of cisplatin induced AKI models.CONCLUSION This study has constructed a human kidney organoid model and verified the feasibility of human kidney organoids being used to simulate AKI induced by chemotherapy drugs in vitro.Kim-1 combined with IL-8 is expected to provide data for clinical prediction of the possibility of AKI induced by such drugs and countermeasures against adverse reactions.关键词
急性肾损伤/肾类器官/顺铂/药物筛选Key words
acute kidney injury/kidney organoids/cisplatin/drug screening分类
医药卫生引用本文复制引用
马瑞麟,吴成君,岳亮,贠志敏,楼张蓉,刘琦,崔宏图,钟鹏飞,高卓,檀英霞..基于人肾类器官构建顺铂诱导急性肾损伤模型[J].中国药理学与毒理学杂志,2024,38(4):279-285,7.
