摘要
目的 观察氧化苦参碱(oxymatrine,OMT)通过免疫负调控机制对小鼠胶原诱导性关节炎(collagen-induced arthritis,CIA)的缓解作用。方法 将DBA/1J小鼠随机分为正常组、模型组、OMT组和地塞米松组,每组9只。采用胶原和佐剂等体积混合背部皮下多点注射诱导DBA/1J小鼠,构建CIA小鼠模型。OMT组和地塞米松组分别用氧化苦参碱和地塞米松进行腹腔注射,正常组注射同等剂量的生理盐水。采用实时荧光定量PCR(RT-qPCR)法检测脾淋巴细胞叉头样转录因子P3(forkhead box protein3,Foxp3)、细胞毒性T淋巴细胞相关蛋白-4(cytotoxic T-lymphocyte-associated protein-4,CTLA-4)和程序性死亡受体-1(programmed cell death protein-1,PD-1)的mRNA表达水平。采用苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察关节滑膜组织的异位生发中心。采用免疫组织化学法和Western blot检测Foxp3及CTLA-4和PD-1的表达。结果 OMT可缓解CIA小鼠关节肿胀度并降低其关节评分,增加脾淋巴细胞和关节组织Foxp3及CTLA-4的表达,降低PD-1的表达(P均<0.05),并减少炎性细胞大面积浸润。结论 OMT可能经增加调节性(Foxp3+)T细胞CTLA-4的表达但降低PD-1的表达而缓解RA。
Objective To observe the effect of oxymatrine(OMT)on the remission of collagen-induced arthritis(CIA)in mice through negative immune regulation mechanism.Methods DBA/1J mice were randomly divided into normal group,model group,OMT group and dexamethasone group,with 9 mice in each group.DBA/1J mice were induced by subcutaneous multi-point injection of collagen and adjuvant in the back,and the CIA model was constructed.The OMT group and dexamethasone group were intraperitoneal injected with oxymatrine and dexamethasone respectively,and the normal group was injected with the same dose of normal saline.The mRNA expression levels of Foxp3,CTLA-4 and PD-1 in spleen lymphocytes were detected by RT-qPCR.HE staining was used to observe the ectopic geriatric center of joint synovium.The expressions of Foxp3,CTLA-4 and PD-1 were examined by immunohistochemistry and Western blot.Results OMT could significantly relieve the joint swelling degree and reduce the joint score of CIA mice,significantly increase the expression of Foxp3 and CTLA-4 in spleen lymphocytes and joints,but decrease the expression of PD-1(P all<0.05),and reduce the large-scale inflammatory cell infiltration.Conclusion OMT may alleviate rheumatoid arthritis by increasing the expression of CTLA-4 on regulatory(Foxp3+)T cells but decreasing the expression of PD-1.
作者
岳晓琪
牛腾耀
詹静慧
高强
张艳丽
YUE Xiaoqi;NIU Tengyao;ZHAN Jinghui;GAO Qiang;ZHANG Yanli(Department of Pathogenic Biology and Medical Immunology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China)
出处
《宁夏医科大学学报》
2023年第3期224-229,共6页
Journal of Ningxia Medical University
基金
国家自然科学基金项目(82160780)。