摘要
目的 探讨CXCR3抑制剂对小鼠类风湿关节炎(RA)的治疗作用及其相关机制。方法 将30只BALB/C小鼠随机分为对照组、模型组和治疗组。通过骨胶原诱导法建立小鼠RA模型,造模成功后,治疗组灌胃CXCR3抑制剂SCH 546738(1 mg·kg^(-1)·d^(-1)),对照组和模型组给予相同体积生理盐水,持续4周。每周记录小鼠关节炎指数评分。采用实时PCR和Western blotting检测各组小鼠关节组织肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)和白细胞介素-1β(IL-1β)表达,采用流式细胞术检测外周血中Th1/Th2细胞比例,采用ELISA检测血清中IFN-γ和IL-4水平。分离小鼠外周血CD4^(+)T细胞,并分为CD4^(+)T组和CD4^(+)T+SCH 546738组(与SCH546738共孵育)。采用流式细胞术检测Th1/Th2细胞比例。结果 与对照组相比,模型组小鼠关节炎指数评分升高,关节组织TNF-α、IFN-γ和IL-1β mRNA和蛋白表达升高,外周血Th1/Th2细胞比例升高,血清中IFN-γ水平升高(均P<0.05)。与模型组相比,治疗组小鼠关节炎指数评分降低,关节组织TNF-α、IFN-γ和IL-1β m RNA和蛋白表达降低,外周血Th1/Th2细胞比例降低,血清中IFN-γ水平降低(均P<0.05)。与CD4^(+)T组相比,CD4^(+)T+SCH 546738组Th1/Th2细胞比例降低(P<0.001)。结论 CXCR3抑制剂通过降低Th1/Th2细胞比例,改善体内免疫反应,从而缓解小鼠RA的疾病进展。
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 treatment 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 expression of TNF-α,IFN-γ,and IL-1βin 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-γand 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-γlevels(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-γlevels(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 alleviate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.
作者
黄立敬
陈子聪
杨春春
井雨
聂文佳
HUANG Lijing;CHEN Zicong;YANG Chunchun;JING Yu;NIE Wenjia(Department of Rheumatology and Immunology,The First Hospital of Hebei Medical University,Shijiazhuang 050030,China;Gastrointestinal Disease Diagnosis and Treatment Center,The First Hospital of Hebei Medical University,Shijiazhuang 050030,China)
出处
《中国医科大学学报》
北大核心
2025年第9期796-801,共6页
Journal of China Medical University
基金
河北省医学科学研究课题(20231005)。
