中国医科大学学报2025,Vol.54Issue(9):796-801,6.DOI:10.12007/j.issn.0258-4646.2025.09.006
CXCR3抑制剂对小鼠类风湿关节炎的治疗作用及机制
Therapeutic effect and mechanism of CXCR3 inhibitor in rheumatoid arthritis in mice
摘要
Abstract
Objective To investigate the therapeutic effect and underlying mechanism of action of a CXCR3 inhibitor in rheumatoid arthritis(RA)in mice model.Methods Thirty BALB/C mice were randomly divided into control,model,and treatment groups.RA model was established in both the model and treatment groups using a collagen induction method.Upon successful modeling,mice in the treat-ment group received a daily oral administration of 1 mg/kg SCH 546738(CXCR3 inhibitor)for 4 weeks,whereas those in the control and model groups received equivalent volumes of saline.During treatment,the weekly arthritis index scores of mice were recorded.The expres-sion of TNF-α,IFN-γ,and IL-1β in joint tissues was determined based on Western blotting and qRT-PCR analyses.In addition,we used flow cytometry to assess peripheral blood Th1/Th2 cell ratios,and serum levels of IFN-γ and IL-4 were measured using ELISA.Peripheral blood CD4+T cells were isolated and co-incubated with SCH 546738,and subsequently assessed as CD4+T and CD4+T+SCH 546738 groups.In addition,Th1/Th2 cell ratios were assessed using flow cytometry.Results Compared with the control group,mice in the model group were characterized by elevated weekly arthritic index scores,increases in the joint tissues expression of TNF-α,IFN-γ,and IL-1β,heightened peripheral blood Th1/Th2 cell ratios,and raised serum IFN-γ levels(P<0.05).In contrast to the model group,the treatment group mice had lower weekly arthritis index scores,reductions in the joint tissue expression of TNF-α,IFN-γ,and IL-1β,diminished peripheral blood Th1/Th2 cell ratios,and lowered serum IFN-γ levels(P<0.05).Moreover,compared with the CD4+T group,the CD4+T+SCH 546738 group was characterized reduced Th1/Th2 cell ratios(P<0.001).Conclusion The CXCR3 inhibitor SCH 546738 can alle-viate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.关键词
CXCR3抑制剂/Th1/Th2细胞比例/类风湿关节炎/免疫Key words
CXCR3 inhibitor/Th1/Th2 cell ratio/rheumatoid arthritis/immunity分类
医药卫生引用本文复制引用
黄立敬,陈子聪,杨春春,井雨,聂文佳..CXCR3抑制剂对小鼠类风湿关节炎的治疗作用及机制[J].中国医科大学学报,2025,54(9):796-801,6.基金项目
河北省医学科学研究课题(20231005) (20231005)