不同缺血时间所致急性肾损伤中的动态细胞变化
Dynamic cellular changes in acute kidney injury caused by different ischemia time.
作者信息
Shan Dan, Wang Yin-Ying, Chang Yuan, Cui Hao, Tao Menghao, Sheng Yixuan, Kang Hongen, Jia Peilin, Song Jiangping
机构信息
Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
出版信息
iScience. 2023 Apr 11;26(5):106646. doi: 10.1016/j.isci.2023.106646. eCollection 2023 May 19.
Ischemia reperfusion injury (IRI), often related to surgical procedures, is one of the important causes of acute kidney injury (AKI). To decipher the dynamic process of AKI caused by IRI (with prolonged ischemia phase), we performed single-cell RNA sequencing (scRNA-seq) of clinically relevant IRI murine model with different ischemic intervals. We discovered that Slc5a2 proximal tubular cells were susceptible to AKI and highly expressed neutral amino acid transporter gene , which was dramatically decreased over the time course. With the usage of mass spectrometry-based metabolomic analysis, we detected that the level of neutral amino acid isoleucine dropped off in AKI mouse plasma metabolites. And the reduction of plasma isoleucine was also verified in patients with cardiac surgery-associated acute kidney injury (CSA-AKI). The findings advanced the understanding of dynamic process of AKI and introduced reduction of isoleucine as a potential biomarker for CSA-AKI.
缺血再灌注损伤（IRI）通常与外科手术相关，是急性肾损伤（AKI）的重要病因之一。为了解析IRI（缺血期延长）所致AKI的动态过程，我们对具有不同缺血时间间隔的临床相关IRI小鼠模型进行了单细胞RNA测序（scRNA-seq）。我们发现溶质载体家族5成员2（Slc5a2）近端肾小管细胞易受AKI影响且高表达中性氨基酸转运蛋白基因，该基因在整个时间进程中显著下降。通过基于质谱的代谢组学分析，我们检测到在AKI小鼠血浆代谢物中中性氨基酸异亮氨酸水平下降。并且在心脏手术相关急性肾损伤（CSA-AKI）患者中也证实了血浆异亮氨酸的降低。这些发现加深了对AKI动态过程的理解，并引入异亮氨酸降低作为CSA-AKI的潜在生物标志物。
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