上海交通大学学报（医学版）2025，Vol.45Issue(10)：1279-1287,9.DOI:10.3969/j.issn.1674-8115.2025.10.003
青蒿琥酯对自发性干燥综合征NOD/Ltj小鼠的治疗作用
Therapeutic effect of artesunate on spontaneous mouse models of Sjögren syndrome(NOD/Ltj mouse)
摘要
Abstract
Objective·To elevate the therapeutic effect of artesunate(ART)on NOD/Ltj mice(non-obese diabetic mice,the spontaneous models of Sjögren 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 Sjögren 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 Naïve 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.关键词
干燥综合征/青蒿琥酯/NOD/Ltj小鼠/B淋巴细胞Key words
Sjögren syndrome(SS)/artesunate(ART)/NOD/Ltj mouse/B lymphocyte分类
医药卫生引用本文复制引用
李燕香,石欢,俞创奇..青蒿琥酯对自发性干燥综合征NOD/Ltj小鼠的治疗作用[J].上海交通大学学报（医学版）,2025,45(10):1279-1287,9.基金项目
国家自然科学基金(82174041) （82174041）
上海市自然科学基金(22ZR1437400) （22ZR1437400）
上海市扬帆计划(22YF1422300). National Natural Science Foundation of China(82174041) （22YF1422300）
Natural Science Foundation of Shanghai(22ZR1437400) （22ZR1437400）
Shanghai Young Science and Technology Talents Sailing Program(22YF1422300). （22YF1422300）
