Wang Xing, Tang Jieyin, Zhang Xianggui, Zeng Huilin
Department of Nephrology and Rheumatology, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, China,
Department of Nephrology and Rheumatology, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, China.
Int Arch Allergy Immunol. 2025;186(4):358-368. doi: 10.1159/000541812. Epub 2024 Nov 5.
Esculentoside A (EsA) is one of the main components of the traditional Chinese medicine Phytolacca esculenta. The possible mechanism of action of EsA in the treatment of lupus nephritis (LN) was explored by observing the effects of EsA on CD19+ IL-35+regulatory B (IL-35+Breg) cells.
Twenty-four MRL/lpr mice were randomly divided into control, EsA, and EsA+IL-12p35 antibody groups. Mice were administered the respective treatments intraperitoneally once a day for 4 weeks. The urine protein/creatinine ratio (UPCR) and blood creatinine (Cr) and IL-35, IL-10, and IL-17 expression levels were measured. Body and spleen weight were measured to calculate the splenic index (SI). Flow cytometry was performed to determine the proportion of CD19+ IL-35+ Breg cells in the spleen. Hematoxylin-eosin and PASM-Masson staining of renal tissues were performed, and the "Austin" acute index (AI) system for LN was determined.
The most severe conditions were seen in mice in the control group, with the highest UPCR, Cr, and IL-17 levels and SI and AI scores; the most severe renal histopathology, and the lowest proportion of CD19+ IL-35+ Breg cells and IL-35 and IL-10 levels. This was followed by the EsA+IL-12p35 antibody group. The EsA group had the lowest UPCR, Cr, and IL-17 levels and SI and AI scores; the mildest renal lesions; and the highest proportion CD19+ IL-35+ Breg cells and IL-35 and IL-10 levels.
EsA delayed the progression of LN by promoting the proliferation of CD19+ IL-35+ Breg cells, upregulating the expression of IL-35, and decreasing the secretion of IL-17.
商陆皂苷甲（EsA）是中药商陆的主要成分之一。通过观察EsA对CD19+IL-35+调节性B（IL-35+Breg）细胞的影响，探讨其治疗狼疮性肾炎（LN）的可能作用机制。
将24只MRL/lpr小鼠随机分为对照组、EsA组和EsA+IL-12p35抗体组。小鼠每天腹腔注射相应治疗药物一次，共4周。检测尿蛋白/肌酐比值（UPCR）、血肌酐（Cr）以及IL-35、IL-10和IL-17的表达水平。测量体重和脾脏重量以计算脾脏指数（SI）。采用流式细胞术测定脾脏中CD19+IL-35+Breg细胞的比例。对肾组织进行苏木精-伊红和PASM- Masson染色，并确定LN的“Austin”急性指数（AI）系统。
对照组小鼠病情最为严重，UPCR、Cr和IL-17水平最高，SI和AI评分最高；肾脏组织病理学最严重，CD19+IL-35+Breg细胞比例以及IL-35和IL-10水平最低。其次是EsA+IL-12p35抗体组。EsA组UPCR、Cr和IL-17水平以及SI和AI评分最低；肾脏病变最轻；CD19+IL-35+Breg细胞比例以及IL-35和IL-10水平最高。
EsA通过促进CD19+IL-35+Breg细胞增殖、上调IL-35表达以及减少IL-17分泌，延缓了LN的进展。
