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/Ipr小鼠肾损害

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Abstract：ObjectiveToinvestigatetheeficacyofQihuangJianpi ZishenGranules（QJZ）forinhibitingrenalBcelldiffrentiation inMRL/lprmiceand exploreitsunderlying mechanism.Methods Thirty8-wek-old femaleMRL/lpr mice wererandomly dividedintomodelgroup，QJZgroup，prednisone （Pred）group，QJZ+Pred group，andAIM2inibitorgroup（n=6），ith68- week-oldfemale57BL/6iceastoalotrolgroup.Aftertreatmentsithoalsalie，QJZred，oriitor for8weeks，themice wereexamined forurinarytotal protein-to-creatinineratio （TPCR）andalbumin-to-creatinineratio （ACR），serumreatinine（Cr）andbloodureanitrogen （BUN）levels，andrenalhistopathology（withHE，MassonadP staining）andultastructuralanges （witheectroncroscopy）.EIAimunostocheistryimunofluoresceceaing andflowcytometrywereusedtoetectbloodlevelsofanti-dsDAantibodies，cytokinesandchemokines，renaldepositionof complementcootsdC4leesiosofD19Dnd3dgsisecBe subsets.The effct of QJZ onthe AIM2/Blimp-1/Bcl-6 signaling axiswas examined using Western bloting.ResultsQJZ treatment significantlyimprovedCr，BUN，TPCRandACRinMRL/lpr mice，amelioratedrenal pathologies，reducedthe expressionsofds-DNA，BAFF，IL-21，CXCL12，CXCL13，C3andC4，andincreasedIL-10levels.QJZsignificantly downregulated renal expresions of the key B-celltranscription factors Blimp-1and XBP-1，upregulated Bcl-6and PAX5 expressions，inhibitedB-celldifferentiation，andlowered the expressions of AIM2，CD27，CD138 and CD69. InhibitionofAIM2similarlyreducedrenalBlimp-1and XBP-1 expressions，increased Bcl-6 and PAX5 levels， suppressed B-celldifferentiation，decreasedIgG production，reducedC3andC4deposition，andalleviated renalpathology in MRL/lpr mice. Conclusion QJZ inhibits Bcell differentiationand alleviatesrenal damage insystemiclupuserythematosuspossiblybysuppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.

Keywords： Qihuang Jianpi Zishen Granules; systemic lupus erythematosus; renal damage; Bcells; AIM2/Blimp1/Bcl-6

系统性红斑狼疮（SLE）是自身免疫介导的以免疫性炎症为突出表现的弥漫性结缔组织病，常累及肾脏，继而发展为狼疮肾炎（LN）[12]。（剩余16363字）