南方医科大学学报2024，Vol.44Issue(3)：465-473,9.DOI:10.12122/j.issn.1673-4254.2024.03.07
健脾滋肾方抑制系统性红斑狼疮患者的足细胞自噬:基于网络药理学和临床研究
Jianpi Zishen granule inhibits podocyte autophagy in systemic lupus erythematosus:a network pharmacology and clinical study
摘要
Abstract
Objective To explore the therapeutic mechanism of Jianpi Zishen(JPZS)granules for systemic lupus erythematosus(SLE)in light of podocyte autophagy regulation.Methods TCMSP,GeneCards,OMIM,and TTD databases were used to obtain the targets of JPZS granules,SLE,and podocyte autophagy.The protein-protein interaction network was constructed using Cytoscape,and the key active ingredients and targets were screened for molecular docking.In the clinical study,46 patients with SLE were randomized into two groups to receive baseline treatment with prednisone acetate and mycophenolate mofetil(control group)and additional treatment with JPZS granules(observation group)for 12 weeks,with 10 healthy volunteers as the healthy control group.Urinary levels of nephrin and synaptopodin of the patients were detected with ELISA.Western blotting was performed to determine peripheral blood levels of p-JAK1/JAK1,p-STAT1/STAT1,LC3Ⅱ/LC3I,and p62 proteins of the participants.Results Four key active ingredients and 5 core target genes(STAT1,PIK3CG,MAPK1,PRKCA,and CJA1)were obtained,and enrichment analysis identified the potentially involved signaling pathways including AGE-RAGE,JAK/STAT,EGFR,and PI3K/Akt.Molecular docking analysis showed that STAT1 was the most promising target protein with the highest binding activity,suggesting its role as an important mediator for signal transduction after JPZS granule treatment.In the 43 SLE patients available for analysis,treatment with JPZS granule significantly reduced serum levels of p-JAK1/JAK1,p-STAT1/STAT1,and LC3Ⅱ/LC3I(P<0.05 or 0.01),increased the protein level of P62(P<0.05),and reduced urinary levels of nephrin and synaptopodin(P<0.05).Conclusion The therapeutic effect of JPZS granules on SLE is mediated probably by coordinated actions of quercetin,kaempferol,β-sitosterol,and isorhamnetin on their target gene STAT1 to inhibit the JAK/STAT pathway,thus suppressing autophagy and alleviating podocyte injuries in SLE.关键词
系统性红斑狼疮/健脾滋肾方/网络药理学/足细胞/自噬Key words
systemic lupus erythematosus/Jianpi Zishen granules/network pharmacology/podocytes/autophagy引用本文复制引用
陈君洁,黄传兵,李明..健脾滋肾方抑制系统性红斑狼疮患者的足细胞自噬:基于网络药理学和临床研究[J].南方医科大学学报,2024,44(3):465-473,9.基金项目
国家自然科学基金(81473672) （81473672）
安徽省临床医学研究转化专项项目(202304295107020114) （202304295107020114）
大健康研究院新安医学与中医药现代化研究所专项资金资助(2023CXMMTCM015) （2023CXMMTCM015）
2022年度国家级中医优势专科建设项目-风湿病科 （）
安徽省卫生健康科研项目重点项目(AHWJ2022a005) （AHWJ2022a005）
安徽省高校协同创新项目(GXXT-2021-085) （GXXT-2021-085）
安徽省教育厅研究生创新创业实践项目(ahzyydx-tb83)Supported by National Natural Science Foundation of China(81473672). （ahzyydx-tb83）
