南方医科大学学报2026，Vol.46Issue(4)：785-793,9.DOI:10.12122/j.issn.1673-4254.2026.04.07
健脾滋肾方改善系统性红斑狼疮小鼠肾损害:基于p53-MDM2信号轴介导的铁死亡
Jianpi Zishen Formula improves renal damage in mice with systemic lupus erythematosus by inhibiting p53-MDM2 signaling axis-mediated ferroptosis
摘要
Abstract
Objective To investigate the therapeutic mechanism of Jianpi Ziren Formula(JPZS)for ameliorating renal injury in mice with systemic lupus erythematosus(SLE).Methods Thirty MRL/lpr lupus mice were randomly divided into model group,JPZS treatment group,and prednisone treatment group,with 10 C57BL/6 mice as the control group.After treatment with daily gavage with normal saline,JPZS(7.8 g/kg)or prednisone(5 mg/kg)for 8 consecutive weeks,the mice were examined for changes in serum levels of anti-ds DNA,C3 and Scr,24-h urine protein(24hPRO)and renal Fe2+content,MDA level,SOD activity,GSH level,and ROS level.Renal histopathological changes and ultrastructural changes were observed with HE staining and transmission electron microscopy.The changes in renal expressions of p53,MDM2,GPX4,SLC7A11,ACSL4,Bax,Bcl-2,and caspase-3 mRNAs and proteins were detected using RT-qPCR and Western blotting.Results Compared with the normal control mice,the mouse models of SLE had significantly elevated levels of dsDNA,Scr,24hPRO,Fe²⁺,MDA,and ROS,increased renal expressions of p53,MDM2,ACSL4,Bax,and caspase-3,lowered levels of C3,SOD,and GSH,and reduced renal expressions of GPX4,SLC7A11,and Bcl-2 at both the mRNA and protein levels.Treatment with JPZS and prednisone both significantly ameliorated these abnormalities in the mouse models.Conclusion JPZS can reduce renal ferroptosis in lupus mice,ameliorate kidney injury,and promote renal function repair possibly by inhibiting the p53-MDM2 signaling axis,which is closely associated with regulation of glomerular podocyte ferroptosis.关键词
系统性红斑狼疮/肾损害/健脾滋肾方/铁死亡/p53-MDM2信号轴Key words
systemic lupus erythematosus/kidney damage/Jianpi Zishen Formula/ferroptosis/p53-MDM2 signaling axis引用本文复制引用
李云飞,黄传兵,庞利君,朱子衡,李明..健脾滋肾方改善系统性红斑狼疮小鼠肾损害:基于p53-MDM2信号轴介导的铁死亡[J].南方医科大学学报,2026,46(4):785-793,9.基金项目
国家自然科学基金(82574970,82104782) （82574970,82104782）
安徽省临床医学研究转化专项项目(202304295107020114,202304295107020115) （202304295107020114,202304295107020115）
大健康研究院新安医学与中医药现代化研究所专项(2023CXMMTCM015) Supported by National Natural Science Foundation of China(82574970,82104782). （2023CXMMTCM015）
