北京中医药大学学报2026,Vol.49Issue(7):922-935,14.DOI:10.3969/j.issn.1006-2157.2026.07.006
从Th1/Th2/Th17细胞免疫失衡探讨四逆散对Graves病的干预机制
Mechanisms of Sini Powder intervention in Graves' disease based on Th1/Th2/Th17 cells immune imbalance
摘要
Abstract
Objective To investigate the effects of Sini Powder on Graves' disease(GD)model mice and to explore its mechanism in regulating Th1/Th2/Th17 cells immune imbalance at three levels:immune center(spleen),humoral circulation(serum),and target organ(thyroid).Methods Twenty-four female BALB/c mice were randomly divided into normal group(n=6)and modeling group(n=18)using a randomized block design.GD model was established through intramuscular injection of Ad-TSHR289 adenovirus.After successful modeling,GD mice were randomly assigned to the model,methimazole(4.55×10-3 g/kg),and Sini Powder(5.46 g/kg)groups using random number table,with corresponding interventions administered daily for 6 weeks.HE staining was used to assess pathological changes in thyroid follicular epithelial cells;serum levels of thyrotropin receptor antibody(TRAb)and thyroxine(T4)were measured using radioimmunoassay.The proportions of Th1,Th2,and Th17 cells in spleen tissues were analyzed by flow cytometry;mRNA and protein expressions of Th1-derived interferon-γ(IFN-γ),Th2-derived interleukin-4(IL-4),and Th17-derived interleukin-17A(IL-17A)in spleen were detected by quantitative reverse transcription PCR and Western blotting.Serum levels of IFN-γ,IL-4,IL-10,IL-17A,as well as regulated on activation,normal T-cell expressed and secreted(RANTES),macrophage inflammatory protein-1β(MIP-1β),and monocyte chemoattractant protein-1(MCP-1)were measured using Luminex protein biochip assay.Immunohistochemistry was performed to localize and assess the expression of IFN-γ,IL-4,and IL-17A in thyroid tissues.Results Sini Powder reduced thyroid volume of model mice,as well as decreased serum TRAb and T4 levels(P<0.01),ameliorated pathological damage to thyroid follicular structures,and alleviated splenomegaly.Mechanistic studies revealed that compared with the normal group,the model group exhibited increased trends of the proportions of Th1 and Th17 cells,along with an elevated Th1/Th2 ratio,whereas Th2 cell proportion decreased.Expressions of IFN-γ and IL-17A mRNA,as well as IFN-γ protein expression in spleen increased(P<0.01),with an upward trend in IL-17A protein expression,while IL-4 mRNA expression was downregulated(P<0.01).The serum levels of IFN-γ,IL-10,and RANTES elevated(P<0.01),with upward trends in IL-17A,MIP-1β,and MCP-1,and a downward trend in IL-4 level.The expressions of IFN-γ,IL-4,and IL-17A in thyroid tissues increased.These findings suggest the presence of Th1/Th2/Th17 cells immune imbalance in GD model mice.The methimazole and Sini Powder modulated expressions of IFN-γ,IL-4,and IL-17A in spleen,thyroid,and serum,as well as regulated the expression of chemokines including RANTES,MIP-1β,and MCP-1 of the GD model mice.Conclusion Sini Powder may exert intervention effect on goiter induced by GD via regulating Th1/Th2/Th17 cells immune imbalance and modulating chemokines such as RANTES,MIP-1β,and MCP-1.关键词
四逆散/Graves病/甲状腺肿大/免疫失衡/小鼠Key words
Sini Powder/Graves' disease/goiter/immune imbalance/mice分类
医药卫生引用本文复制引用
闫淑鑫,贾雯雯,颜雪,黄敏雪,程云哲,袁慧敏,马文欣,朱晓云,汤阳..从Th1/Th2/Th17细胞免疫失衡探讨四逆散对Graves病的干预机制[J].北京中医药大学学报,2026,49(7):922-935,14.基金项目
国家自然科学基金项目(No.82474487,82004337) (No.82474487,82004337)
中央高校基本科研业务费自主选题(No.2020-JYB-XJSJJ-002) National Natural Science Foundation of China(Nos.82474487 and 82004337) (No.2020-JYB-XJSJJ-002)