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 and glomerular filtrate flow were circulating simultaneously, 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.

在这项研究中，我们开发了一种多层微流体装置来模拟肾单位，它是由“肾小球”，“鲍曼氏囊”，“近端管状内腔”和“房周毛细血管”形成的。在这种微型设备中，人造肾血流和肾小球滤出液流同时循环，模仿了肾单位的行为。。在这个动态的人工肾中，我们观察了典型的肾脏生理，包括肾小球大小选择屏障，肾小球基底膜电荷选择屏障，葡萄糖重吸收和对氨基马尿酸分泌。为了证明我们的微型设备的功能，我们使用它来研究药物诱发的急性肾损伤（AKI）的病理生理，并评估药物诱发的肾毒性，并以顺铂和阿霉素为模型药物。在实验中 我们将“阿霉素”或“顺铂”加载到“肾脏血流”中，通过荧光成像记录初级肾小球内皮细胞，足细胞，肾小管上皮细胞和肾小管周围内皮细胞的损伤，并确定时间依赖性，剂量依赖性和死亡顺序四种类型的肾细胞。然后，通过测量多种生物标记物，包括E-钙黏着蛋白，VEGF，VCAM-1，Nephrin和ZO-1，我们研究了由阿霉素或顺铂引起的细胞损伤机制。此外，我们研究了“肾血流”中BSA对阿霉素或顺铂诱导的肾毒性的影响，发现BSA增强了细胞之间的紧密连接并缓解了顺铂诱导的肾毒性。此外，我们比较了肾单位模型和传统的肾小管模型，以评估药物引起的肾毒性。