感染、炎症、修复2026，Vol.27Issue(1)：8-18,11.DOI:10.3969/j.issn.1672-8521.2026.01.002
脓毒症相关急性肾损伤免疫细胞动态变化及其在炎症与组织修复中的作用
Dynamic changes of immune cells in sepsis-associated acute kidney injury and their role in inflammation and tissue repair
摘要
Abstract
Objective To investigate the dynamic changes of immune cells and the characteristics of the renal immune microenvironment under impaired renal function during sepsis-associated acute kidney injury(S-AKI).Methods Eighteen male C57BL/6J mice aged 6-8 weeks were selected.An S-AKI model was established by cecal ligation and puncture combined with low-dose lipopolysaccharide injection.Mice were randomly divided into the healthy control group,the S-AKI Day 2(S-AKI_D2)group,and the S-AKI Day 7(S-AKI_D7)group,with 6 mice in each group.Hematoxylin-eosin(HE)staining and Masson's trichrome staining were used to evaluate the degree of renal injury.Renal tissue microstructural alterations were examined using transmission electron microscopy.Single-cell RNA sequencing(scRNA-seq)was further employed to systematically analyze the single-cell transcriptomic characteristics of the renal immune microenvironment during the early injury phase(D2)and repair phases(D7),with a focus on functional changes of neutrophils and macrophages during the inflammatory responses and tissue repair processes.Results Compared with the healthy control group,the S-AKI(D2)group exhibited massive infiltration of activated neutrophils in renal tissue.scRNA-seq analysis revealed that both the absolute number and proportion of neutrophils were higher in the in the S-AKI_D2 group than in the healthy control group.This subpopulation highly expressed inflammation-related surface markers and exhibited downregulation of apoptosis-related genes,suggesting delayed apoptosis and sustained promotion of renal inflammation.By day 7(D7),the number of macrophages significantly increased,notably driven by expansion of tissue-repairing macrophage subpopulations highly expressing anti-inflammatory phenotype markers like Arg1 and Mrc1.This increase actively promoted inflammation resolution and tissue repair,shifting the renal microenvironment from inflammation to repair.Conclusions During S-AKI,immune cell populations undergo dynamic evolution,exerting a dual impact on renal injury and repair.By precisely targeting the temporal functional shift of neutrophils and macrophages across different stages,and by specifically modulating early neutrophil overactivation or enhancing the function of reparative macrophages,it is possible to optimize the inflammation-repair balance.This approach holds promise for significantly improving patient survival rates and quality of life.关键词
肾脏/免疫微环境/脓毒症/急性肾损伤/单细胞RNA测序/巨噬细胞/中性粒细胞Key words
kidney/immune microenvironment/sepsis/acute kidney injury/single-cell RNA sequencing/macrophage/neutrophil引用本文复制引用
曹超,徐静,李然然,刘嘉琳,瞿洪平..脓毒症相关急性肾损伤免疫细胞动态变化及其在炎症与组织修复中的作用[J].感染、炎症、修复,2026,27(1):8-18,11.基金项目
国家自然科学基金资助项目(82372203,82270004) （82372203,82270004）
上海市自然科学基金资助项目(23ZR1439800,24ZR1445800) （23ZR1439800,24ZR1445800）
中国博士后科学基金(2024M762043) （2024M762043）
