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对比剂所致肾损伤的三维肾芯片评估：渗透压和黏度

Three-Dimensional Kidney-on-a-Chip Assessment of Contrast-Induced Kidney Injury: Osmolality and Viscosity.

作者信息

Kim Kipyo, Jeong Beomgyun, Lee Yun-Mi, Son Hyung-Eun, Ryu Ji-Young, Park Seokwoo, Jeong Jong Cheol, Chin Ho Jun, Kim Sejoong

机构信息

Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University College of Medicine, Incheon 22332, Korea.

Research Center for Materials Analysis, Korea Basic Science Institute, Daejeon 34133, Korea.

出版信息

Micromachines (Basel). 2022 Apr 28;13(5):688. doi: 10.3390/mi13050688.

DOI:10.3390/mi13050688
PMID:35630155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9146534/
Abstract

Increased viscosity of concentrated contrast media (CM) in the renal tubules can perturb renal hemodynamics and have a detrimental effect on tubular epithelial cells. However, the effects of viscosity on contrast-induced nephropathy (CIN) remain poorly understood. Conventional in vitro culture studies do not reflect the rheological properties of CM. Therefore, we investigated the effects of CM viscosity on renal tubules using a kidney-on-a-chip and two different types of CM. Renal proximal tubule epithelial cells (RPTEC) were cultured in a three-dimensional microfluidic culture platform under bidirectional fluid shear stress. We treated the RPTEC with two types of CM: low- (LOCM, iopromide) and iso-osmolar contrast media (IOCM, iodixanol). Renal tubular cell injury induced by LOCM and IOCM was examined under different iodine concentrations (50-250 mgI/mL) and shear-stress conditions. LOCM showed a significant dose-dependent cytotoxic effect, which was significantly higher than that of IOCM under static and low-to-moderate shear stress conditions. However, high shear-stress resulted in reduced cell viability in IOCM; no difference between IOCM and LOCM was found under high shear-stress conditions. The cytotoxic effects were pronounced at a mean shear stress of 1 dyn/cm or higher. The high viscosity of IOCM slowed the fluid flow rate and augmented fluid shear-stress. We suggest an alternative in vitro model of CIN using the three-dimensional kidney-on-a-chip. Our results indicate a vital role of viscosity-induced nephrotoxicity under high shear-stress conditions, contrary to the findings of conventional in vitro studies.

摘要

肾小管中高浓度造影剂（CM）的粘度增加会扰乱肾脏血流动力学，并对肾小管上皮细胞产生有害影响。然而，粘度对造影剂肾病（CIN）的影响仍知之甚少。传统的体外培养研究无法反映CM的流变学特性。因此，我们使用芯片肾脏和两种不同类型的CM，研究了CM粘度对肾小管的影响。肾近端小管上皮细胞（RPTEC）在双向流体剪切应力下，培养于三维微流控培养平台中。我们用两种类型的CM处理RPTEC：低渗（LOCM，碘普罗胺）和等渗造影剂（IOCM，碘克沙醇）。在不同碘浓度（50 - 250 mgI/mL）和剪切应力条件下，检测LOCM和IOCM诱导的肾小管细胞损伤。在静态和低至中等剪切应力条件下 LOCM 显示出显著的剂量依赖性细胞毒性作用，显著高于IOCM。然而，高剪切应力导致IOCM中的细胞活力降低；在高剪切应力条件下，IOCM和LOCM之间未发现差异。在平均剪切应力为1 dyn/cm或更高时，细胞毒性作用明显。IOCM的高粘度减缓了流体流速并增加了流体剪切应力。我们提出了一种使用三维芯片肾脏的CIN体外替代模型。我们的结果表明，与传统体外研究结果相反，在高剪切应力条件下，粘度诱导的肾毒性起着至关重要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/7335e3f73a42/micromachines-13-00688-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/9b91d35e3597/micromachines-13-00688-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/f61b44ef14ae/micromachines-13-00688-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/0e74acaef1df/micromachines-13-00688-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/7335e3f73a42/micromachines-13-00688-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/9b91d35e3597/micromachines-13-00688-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/f61b44ef14ae/micromachines-13-00688-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/0c1ec61cc13a/micromachines-13-00688-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/38084b89b3e9/micromachines-13-00688-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/0e74acaef1df/micromachines-13-00688-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f062/9146534/7335e3f73a42/micromachines-13-00688-g006.jpg

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