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一种基于低渗造影剂的新型对比剂诱导急性肾损伤小鼠模型。

A novel contrast-induced acute kidney injury mouse model based on low-osmolar contrast medium.

机构信息

Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Nephrology, Lianshui People's Hospital, Lianshui, China.

出版信息

Ren Fail. 2022 Dec;44(1):1345-1355. doi: 10.1080/0886022X.2022.2108449.

Abstract

The contrast-induced acute kidney injury (CI-AKI) has been becoming the third common cause of hospital-acquired acute kidney injury. An ideal animal model is essential for understanding the pathophysiology of CI-AKI. Previous CI-AKI studies were mostly performed on rats with high-osmolar contrast medium (HOCM), which is unsuitable for transgenic researches. This study provides a novel, efficient and reproducible CI-AKI model which was developed in mouse by administrating a low-osmolar contrast medium (LOCM). First of all, we applied the frequently used pretreatments (uninephrectomy and water deprivation), which combined with HOCM on rats could induce CI-AKI, on mice with LOCM. Secondly, we attempted to find a novel pretreatment suitable for mouse and LOCM by combining two classic pretreatments(uninephrectomy, water deprivation and furosemide administration). Finally, we evaluate the kidney damage of the novel model. We found that this mouse model possessed a significant reduction in renal function, severe renal tissue damage, and increased renal tubular cells apoptosis, indicating that LOCM is a feasible inducer for CI-AKI mice model. Taken together, we found that uninephrectomy (UPHT) combined with 24 h water deprivation and furosemide administration 20 min before LOCM (iohexol, 10 ml/kg) application is a feasible pretreatment to establish a novel CI-AKI mouse model.

摘要

对比剂诱导的急性肾损伤(CI-AKI)已成为医院获得性急性肾损伤的第三大常见原因。理想的动物模型对于理解 CI-AKI 的病理生理学至关重要。以前的 CI-AKI 研究大多是在使用高渗对比剂(HOCM)的大鼠上进行的,这对于转基因研究来说并不合适。本研究提供了一种新的、高效且可重复的 CI-AKI 模型,该模型是通过在小鼠中给予低渗对比剂(LOCM)开发的。首先,我们应用了常用于大鼠的预处理方法(单侧肾切除和限水),这些预处理方法与 HOCM 联合使用可诱导 CI-AKI,然后在小鼠中应用 LOCM。其次,我们试图通过结合两种经典预处理(单侧肾切除、限水和呋塞米给药)找到一种适合小鼠和 LOCM 的新预处理方法。最后,我们评估了该新型模型的肾脏损伤。结果发现,该小鼠模型的肾功能显著下降,肾脏组织损伤严重,肾小管细胞凋亡增加,表明 LOCM 是诱导 CI-AKI 小鼠模型的一种可行诱导剂。总之,我们发现单侧肾切除(UPHT)联合 24 小时限水和呋塞米给药 20 分钟,然后给予 LOCM(iohexol,10ml/kg)是建立新型 CI-AKI 小鼠模型的一种可行预处理方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/400a/9367657/3c0be3d3cdde/IRNF_A_2108449_F0001_B.jpg

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