氧化苦参碱经Bcl-6/CXCR5信号调控CIA小鼠Tfh-B细胞的实验研究  

Study of oxymatrine on regulating Tfh-B cells in CIA mice via Bcl-6/CXCR5 signal pathway

作　　者：崔振华 王佩佩 詹静慧 摆茹[1] 张艳丽[1] CUI Zhen-Hua;WANG Pei-Pei;ZHAN Jing-Hui;BAI Ru;ZHANG Yan-Li(Department of Pathogen Biology and Immunology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院病原生物学与免疫学系,银川750004

出　　处：《中国免疫学杂志》2021年第19期2351-2356,共6页Chinese Journal of Immunology

基　　金：宁夏自然科学基金(2020AAC03180)资助。

摘　　要：目的:初步探讨氧化苦参碱(OMT)通过Bcl-6/CXCR5信号通路调控胶原诱导关节炎(CIA)小鼠Tfh-B细胞的免疫学机制。方法:28只雄性DBA/1J小鼠随机分为正常对照组、CIA模型组、地塞米松(DXMS)组、OMT组,每组各7只。构建CIA模型并按分组方案给予药物腹腔注射,正常对照组注射等量生理盐水,1次/d,直至第45天结束模型。测量关节肿胀度和关节炎评分,采用ELISA方法测定小鼠血清CII-Ab、IL-21、IL-10及TGF-β水平;HE染色观察小鼠关节病理变化,IHC方法检测其关节滑膜组织Bcl-6及CXCR5的表达;测定脾指数;流式细胞术检测脾Tfh、B细胞的比例;RT-qPCR测定脾单个核细胞Bcl-6、Blimp-1 mRNA的转录水平。结果:OMT可明显缓解减轻CIA小鼠关节炎症,改善关节滑膜增生及软骨破坏,减少炎症细胞浸润;上调关节滑膜组织Bcl-6、CXCR5的表达。下调CIA小鼠血清CII-Ab、IL-21的表达水平而上调IL-10、TGF-β水平;降低脾指数,减少脾Tfh及B细胞的比例,下调脾单个核细胞Bcl-6 mRNA的表达而上调Blimp-1 mRNA的表达。结论:OMT可能经Bcl-6/CXCR5信号通路调控Tfh-B细胞反应从而减缓类风湿性关节炎(RA)的发生与进展。Objective:To investigate the immunological mechanism of oxymatrine(OMT)regulating Tfh-B cells in collageninduced arthritis(CIA)through Bcl-6/CXCR5 signal pathway.Methods:28 cases of male DBA/1J mice were randomly divided into normal control group,CIA model group,dexamethasone(DXMS)group and OMT group,7 cases in each group.The CIA model was established,and the drugs were injected according to the plan,the normal group was injected with the same amount of normal saline,once a day,until the 45th day.The expression of CII-Ab,IL-21,IL-10 and TGF-βwas detected by ELISA.The pathological changes of joints were observed by HE staining,and the expression of Bcl-6 and CXCR5 in synovium was detected by IHC.The spleen index was measured,the proportion of spleen Tfh and B cells were analyzed by flow cytometry,the mRNA expression of Bcl-6 and Blimp-1 in spleen mononuclear cells was detected by RT-qPCR.Results:OMT significantly alleviated the paw swelling and reduced arthritic score,relieved articular cartilage destruction and synovial hyperplasia in CIA mice.The spleen index was reduced by OMT,the pro-portion of Tfh and B cells were markedly decreased,and the mRNA expression of Bcl-6 were down-regulated but the Blimp-1 were upregulated.Conclusion:OMT may ameliorate the onset and development of rheumatoid arthritis by regulating Tfh and B cells through the Bcl-6/CXCR5 signal pathway.

关 键 词：氧化苦参碱 BCL-6 CXCR5 BLIMP-1 

分 类 号：R392.8[医药卫生—免疫学]