南方医科大学学报2025，Vol.45Issue(11)：2297-2308,12.DOI:10.12122/j.issn.1673-4254.2025.11.02
芪黄健脾滋肾颗粒通过AIM2/Blimp-1/Bcl-6轴抑制B细胞分化改善MRL/lpr小鼠肾损害
Qihuang Jianpi Zishen Granules improves renal damage in MRL/lpr mice by inhibiting B cell differentiation via the AIM2/Blimp-1/Bcl-6 axis
摘要
Abstract
Objective To investigate the efficacy of Qihuang Jianpi Zishen Granules(QJZ)for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism.Methods Thirty 8-week-old female MRL/lpr mice were randomly divided into model group,QJZ group,prednisone(Pred)group,QJZ+Pred group,and AIM2 inhibitor group(n=6),with 6 8-week-old female C57BL/6 mice as the normal control group.After treatments with normal saline,QJZ,Pred,or AIM2 inhibitor for 8 weeks,the mice were examined for urinary total protein-to-creatinine ratio(TPCR)and albumin-to-creatinine ratio(ACR),serum creatinine(Cr)and blood urea nitrogen(BUN)levels,and renal histopathology(with HE,Masson,and PAS staining)and ultrastructural changes(with electron microscopy).ELISA,immunohistochemistry,immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies,cytokines and chemokines,renal deposition of complement components C3 and C4,renal expressions of AIM2,CD19,CD27 and CD138,and changes in splenic B lymphocyte subsets.The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting.Results QJZ treatment significantly improved Cr,BUN,TPCR and ACR in MRL/lpr mice,ameliorated renal pathologies,reduced the expressions of ds-DNA,BAFF,IL-21,CXCL12,CXCL13,C3 and C4,and increased IL-10 levels.QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1,upregulated Bcl-6 and PAX5 expressions,inhibited B-cell differentiation,and lowered the expressions of AIM2,CD27,CD138 and CD69.Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions,increased Bcl-6 and PAX5 levels,suppressed B-cell differentiation,decreased IgG production,reduced C3 and C4 deposition,and alleviated renal pathology in MRL/lpr mice.Conclusion QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.关键词
芪黄健脾滋肾颗粒/系统性红斑狼疮/肾损害/B细胞/AIM2/Blimp-1/Bcl-6Key words
Qihuang Jianpi Zishen Granules/systemic lupus erythematosus/renal damage/B cells/AIM2/Blimp-1/Bcl-6引用本文复制引用
程丽丽,汤忠富,李明,陈君洁,尚双双,刘思娣,黄传兵..芪黄健脾滋肾颗粒通过AIM2/Blimp-1/Bcl-6轴抑制B细胞分化改善MRL/lpr小鼠肾损害[J].南方医科大学学报,2025,45(11):2297-2308,12.基金项目
国家自然科学基金(82574970) （82574970）
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、2023CXMMTCM004) （2023CXMMTCM015、2023CXMMTCM004）
安徽省研究生质量工程研究生创新创业实践项目(2024cxcysj121) （2024cxcysj121）
安徽省高等学校科学重点研究项目(2024AH050957) Supported by National Natural Science Foundation of China(82574970). （2024AH050957）
