时珍国医国药2025，Vol.36Issue(23)：4401-4411,11.DOI:10.70976/j.1008-0805.SZGYGY-2025-2301
昆仙胶囊治疗狼疮性肾炎小鼠的疗效和作用机制研究
Therapeutic effect and mechanism of action of Kunxian Capsule(昆仙胶囊)on lupus nephritis in MRL/lpr mice
摘要
Abstract
Objective To study the effect and molecular mechanism of Kunxian Capsule(昆仙胶囊,KXC)in the treatment of lupus nephritis(LN)mice,and to provide laboratory data support for the clinical application of KXC.Methods The active components of KXC were collected and their targets were predicted using network pharmacology and the TCMSP database.A drug-component-target network was constructed.PPI analysis of the intersecting targets of the drug and disease was performed using the STRING database,fol‐lowed by data integration and enrichment analysis.MRL/lpr mice were randomly divided into a model group,a prednisone acetate group,and low/high-dose KXC groups.All groups received treatment for consecutive 30 days.The 24-hour urinary protein content was detected using biochemical methods.Serum anti-double-stranded DNA(anti-dsDNA)autoantibody levels were measured by ELISA.The open field test was used to assess general health status.Renal pathological changes were observed using HE staining and Masson's trichrome staining.Finally,HK-2 cells were stimulated with IFN-γ.The relative mRNA expression levels of chemokines CXCL10 and CXCL11 after different drug interventions were detected using real-time quantitative PCR(qPCR).Results Network pharmacology screening identified 85 active components and predicted 121 potential target genes for KXC in the treatment of LN.PPI analysis and the association results between active components and the chemokines suggested that KXC might influence LN progression by regulating bio‐logical processes involving the CXCL10/CXCR3 and CXCL11/CXCR3 axes.Compared with the model group,the prednisone acetate group and the low/high-dose KXC groups showed significantly reduced urinary protein concentrations.The prednisone acetate group showed significantly decreased serum anti-dsDNA levels.Both the prednisone acetate group and the low-dose KXC group showed signifi‐cantly lower serum CXCL11 concentrations.HE staining results indicated that the prednisone acetate group and the low-dose KXC group significantly alleviated renal pathological damage.Masson's trichrome staining revealed that the prednisone acetate group and the low/high-dose KXC groups could reduce renal fibrosis to varying degrees.Immunohistochemistry(IHC)showed significantly reduced CXCL11 levels in the low-dose KXC group.qPCR results showed significantly decreased CXCL11 mRNA expression in the prednisone acetate group and the high-dose KXC group(P<0.05).Conclusion KXC can alleviate the clinical symptoms and kidney injury of lupus nephritis by inhibiting the CXCL11/CXCR3 axis,as suggested by network pharmacology prediction and validated by animal and cell experiments.关键词
网络药理学/MRL/Lpr小鼠/昆仙胶囊/狼疮性肾炎/CXCL11/CXCR3轴Key words
Network pharmacology/MRL/lpr mice/Kunxian Capsule(昆仙胶囊)/Lupus nephritis/CXCL11/CXCR3 axis分类
医药卫生引用本文复制引用
李川宁,詹晨光,王茂杰,吴晓东,梅丽艳,覃仁安,杜群群,黄闰月..昆仙胶囊治疗狼疮性肾炎小鼠的疗效和作用机制研究[J].时珍国医国药,2025,36(23):4401-4411,11.基金项目
国家自然科学基金(82404957) （82404957）
广东省科技计划项目(2021B1212050018) （2021B1212050018）
广州中医药大学第二附属医院中医湿证国家重点实验室(SZ2021ZZ35) （SZ2021ZZ35）
中国博士后科学基金(2023M740852) （2023M740852）
