实验动物与比较医学2026，Vol.46Issue(2)：178-190,13.DOI:10.12300/j.issn.1674-5817.2025.175
抗原类型对诱导型干燥综合征小鼠建模的影响
Influence of Antigen Type on the Establishment of an Induced Sjögren Syndrome Mouse Model
摘要
Abstract
Objective This study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome(SS)mouse models,and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic(NOD)/LtJ mice.Methods Adult C57BL/6J mice(equal numbers of males and females)were immunized with submaxillary gland antigen or salivary gland antigen,respectively,combined with Freund's adjuvant to induce SS models.Mice immunized with phosphate-buffered saline(PBS)combined with Freund's adjuvant served as the control group.Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant(FCA)on Days 1 and 7.A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant(FIA)on Day 14.Female NOD/LtJ mice were used as the spontaneous SS model group,with ICR mice as the corresponding control strain for comparative analysis.Body weight,water intake,and salivary flow rate of mice were dynamically monitored for 4 weeks.At the end of the experiment,tissue and serum samples were collected,the weights of submaxillary glands,thymus,and spleen were measured,and organ indices(organ-to-body weight ratios)were calculated.Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin(HE)staining.Serum interleukin-17(IL-17)level was detected using enzyme-linked immunosorbent assay(ELISA).Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A(SSA)and SS type B(SSB)in submaxillary gland tissues.Results Female mice in the submaxillary gland antigen group exhibited significantly increased water intake(P＜0.05)and reduced salivary flow rate(P＜0.05)compared with the female control group.No statistically significant differences were observed in the submaxillary gland index,thymus index and spleen index(P＞0.05).Focal lymphocytic infiltration was observed in the submaxillary glands,and the splenic marginal zone was enlarged.Serum IL-17 levels were significantly increased(P＜0.05).There was no significant difference in submaxillary gland SSA/SSB expression levels(P＞0.05).Compared with the female control group,female mice in the salivary gland antigen group showed no statistically significant differences in water intake,salivary flow rate,submaxillary gland index,and spleen index(P＞0.05),whereas the thymus index was significantly reduced(P＜0.01).Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands,and the splenic white pulp and marginal zone were slightly enlarged.Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased(P＜0.01),whereas no significant change was observed in submaxillary gland SSA expression levels(P＞0.05).Compared with the male control group,mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group,whereas no obvious changes were found in other modeling-related indicators(P＞0.05).Compared with the ICR control group,NOD/LtJ model mice exhibited elevated water intake(P＜0.05),significantly reduced salivary flow rate(P＜0.01),no significant differences in the submaxillary gland index or spleen index(P＞0.05),but a significantly increased thymus index(P＜0.05).Marked focal infiltration was observed in the submaxillary glands,the splenic marginal zone was obviously enlarged,and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased(P＜0.05).Conclusion Submaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice.The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group,but weaker than that in spontaneously SS-prone female NOD/LtJ mice.Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.关键词
干燥综合征/颌下腺抗原/唾液腺抗原/C57BL/6J小鼠/NOD/LtJ小鼠Key words
Sjögren syndrome/Submaxillary gland antigen/Salivary gland antigen/C57BL/6J mice/NOD/LtJ mice分类
生物科学引用本文复制引用
荣文双,牛源菲,刘美婷,杨梦园,崔爽,马丽娜,富尧,王连嵋,曹俊岭..抗原类型对诱导型干燥综合征小鼠建模的影响[J].实验动物与比较医学,2026,46(2):178-190,13.基金项目
国家中医药管理局项目"特色饮片品种挖掘应用-柴胡"(GZY-KJ5-2022-057) （GZY-KJ5-2022-057）
中国中医科学院中药研究所中央级公益性科研院所基本科研业务费专项资金资助项目"中药材拟境栽培与品质保障重点实验室"(ZXKT25043)、"中国中医科学院中药安全用药风险评控与转化重点实验室"(ZXKT25036) （ZXKT25043）
