A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity
文献类型：期刊论文
| 作者 | Qu, Yueyang2,3; An, Fan4; Luo, Yong2,3; Lu, Yao1; Liu, Tingjiao5; Zhao, Weijie2,3; Lin, Bingcheng2,3 |
| 刊名 | BIOMATERIALS
 |
| 出版日期 | 2018-02-01 |
| 卷号 | 155页码:41-53 |
| 关键词 | Nephron Microfluidics Aki Nephrotoxicity |
| ISSN号 | 0142-9612 |
| DOI | 10.1016/j.biomaterials.2017.11.010 |
| 文献子类 | Article |
| 英文摘要 | In this study, we developed a multilayer microfluidic device to simulate nephron, which was formed by "glomerulus", "Bowman's capsule", "proximal tubular lumen" and "peritubular capillary". In this microdevice, artificial renal blood flow was circulating and glomerular filtrate flow was single passing through, mimicking the behavior of a nephron. In this dynamic artificial nephron, we observed typical renal physiology, including the glomerular size-selective barrier, glomerular basement membrane charge-selective barrier, glucose reabsorption and para-aminohippuric acid secretion. To demonstrate the capability of our microdevice, we used it to investigate the pathophysiology of drug-induced acute kidney injury (AKI) and give assessment of drug-induced nephrotoxicity, with cisplatin and doxorubicin as model drugs. In the experiment, we loaded the doxorubicin or cisplatin in the "renal blood flow", recorded the injury of primary glomerular endothelial cells, podocytes, tubular epithelial cells and peritubular endothelial cells by fluorescence imaging, and identified the time-dependence, dose dependence and the death order of four types of renal cells. Then by measuring multiple biomarkers, including E-cadherin, VEGF, VCAM-1, Nephrin, and ZO-1, we studied the mechanism of cell injuries caused by doxorubicin or cisplatin. Also, we investigated the effect of BSA in the "renal blood flow" on doxorubicin-or-cisplatin-induced nephrotoxicity, and found that BSA enhanced the tight junctions between cells and eased cisplatin-induced nephrotoxicity. In addition, we compared the nephron model and traditional tubule models for assessment of drug-induced nephrotoxicity. And it can be inferred that our biomimetic microdevice simulated the complex, dynamic microenvironment of nephron, yielded abundant information about drug-induced-AKI at the preclinical stage, boosted the drug safety evaluation, and provided a reliable reference for clinical therapy. (C) 2017 Elsevier Ltd. All rights reserved. |
| WOS关键词 | ON-A-CHIP ; ISCHEMIA-REPERFUSION INJURY ; CISPLATIN NEPHROTOXICITY ; BIOMARKERS ; HEPATOTOXICITY ; ADRIAMYCIN ; DISEASE ; CELLS ; RATS |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000419539000004 |
| 出版者 | ELSEVIER SCI LTD |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/168544]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Luo, Yong |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian, Peoples R China 2.Dalian Univ Technol, Dept Chem Engn, State Key Lab Fine Chem, Dalian, Peoples R China 3.Dalian Univ Technol, Sch Pharmaceut Sci & Technol, Dalian, Peoples R China 4.Dalian Med Univ, Inst Canc Stem Cell, Dalian, Peoples R China 5.Dalian Med Univ, Coll Stomatol, Dalian, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qu, Yueyang,An, Fan,Luo, Yong,et al. A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity[J]. BIOMATERIALS,2018,155:41-53. |
| APA | Qu, Yueyang.,An, Fan.,Luo, Yong.,Lu, Yao.,Liu, Tingjiao.,...&Lin, Bingcheng.(2018).A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity.BIOMATERIALS,155,41-53. |
| MLA | Qu, Yueyang,et al."A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity".BIOMATERIALS 155(2018):41-53. |
入库方式： OAI收割
来源：大连化学物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。