Therapeutic effect of artesunate on spontaneous mouse models of Sj?gren syndrome(NOD/Ltj mouse)
10.3969/j.issn.1674-8115.2025.10.003
- VernacularTitle:青蒿琥酯对自发性干燥综合征NOD/Ltj小鼠的治疗作用
- Author:
Yanxiang LI
1
;
Huan SHI
1
;
Chuangqi YU
1
Author Information
1. 上海交通大学医学院附属第九人民医院口腔外科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011
- Publication Type:Journal Article
- Keywords:
Sj?gren syndrome(SS);
artesunate(ART);
NOD/Ltj mouse;
B lymphocyte
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2025;45(10):1279-1287
- CountryChina
- Language:Chinese
-
Abstract:
Objective·To elevate the therapeutic effect of artesunate(ART)on NOD/Ltj mice(non-obese diabetic mice,the spontaneous models of Sj?gren syndrome),and explore its potential impact on the distribution of B lymphocyte subsets.Methods·ICR mice were used as the blank control group,and NOD/Ltj mice were randomly divided into disease and ART groups.NOD/Ltj mice and ICR mice were treated with ART(10 mg/kg)or its vehicle(0.5%CMC)by oral gavage every other day for 4 weeks.Body weight,salivary flow rate,submandibular gland index,and spleen index were measured.Cytokines in plasma,including interleukin-6(IL-6),interferon-γ(IFN-γ),and B-cell activating factor(BAFF)in serum,were detected by cytometric bead array(CBA).Hematoxylin-Eosin(H-E)staining of submandibular glands was used to observe the infiltration of lymphocyte.Flow cytometry was applied to analyze the distribution of B lymphocyte subsets in the spleen.The mRNA expression of Prdm1,Il-6r,Il-6,and Stat3 in spleen B lymphocytes was detected by RT-qPCR.The effect of ART on B cells was further detected by CCK-8 and Annexin V-FITC/PI staining by flow cytometry.Results·Compared to the disease group,ART significantly improved the symptoms of Sj?gren syndrome in NOD/Ltj mice.ART treatment also resulted in a reduction in the levels of BAFF,IL-6,and IFN-γ in the plasma(all P<0.05).Moreover,lymphocyte infiltration around the glandular ducts in the submandibular glands was greatly improved in the ART group compared with the disease group.Flow cytometry analysis revealed that the proportion of Na?ve B cells in the ART group was significantly increased compared with the disease group,along with a significant reduction in the proportions of double-negative B cells,switched memory B cells,and plasmablasts(all P<0.05).The relative mRNA expression levels of Prdm1,Il-6r,and Stat3 in the ART group were significantly lower than those in the disease group(all P<0.05).The CCK8 assay results showed that after 6 h of treatment,with the extension of the culture time,cell proliferation in the ART group was significantly inhibited;after 24 h of treatment,the number of apoptotic cells in the ART group was significantly higher than that in the control group(P<0.001).Conclusion·ART demonstrates therapeutic effects in NOD/Ltj mice,potentially through modulating the distribution of peripheral B lymphocyte subsets.It can inhibit the expression of Prdm1,thereby regulating the differentiation of B lymphocytes into plasma cells and plasmablasts.
