条件性免疫反应治疗胶原性关节炎的免疫学机制探讨  

Immunological mechamism of conditioned immune response for treating collagen-induced arthritis in rats

作　　者：王金荣[1] 王宏伟[1] 李秀云[1] 康闽[1] 施虹[1] 刘胜洪[2] 王芳[2] 杨渝珍[3] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,430030 [2]华中科技大学同济医学院基础医学院 [3]华中科技大学同济医学院实验医学研究中心

出　　处：《中国药物与临床》2005年第3期174-178,共5页Chinese Remedies & Clinics

基　　金：国家自然科学基金资助项目(30070722)

摘　　要：目的探讨条件免疫反应治疗胶原性关节炎(CIA)免疫学机制。方法建立大鼠CIA模型。将模型大鼠分为5组:条件免疫反应(CIR)组:以樟脑气味为条件刺激;甲氨蝶呤(MTX)+泼尼松(Pred)为非条件刺激,两者结合7次(7d)后可建立条件免疫反应,然后每日再现条件刺激,每周条件刺激与非条件刺激结合1次,共4周。MTX+Pred组:MTX+Pred治疗4周。MTX+Pred减量组:MTX+Pred治疗,7d内每天1次,7d后每周1次,共4周。单纯闻樟脑气味组:单纯闻樟脑气味4周。空白对照组:安慰剂治疗4周。用流式细胞技术检测大鼠外周血CD4+T淋巴细胞活化(表达CD71)状态,免疫散射比浊法检测大鼠外周血IgG、IgA、IgM、C3、C4、C反应蛋白(CRP)水平,免疫组织化学检测CD68(巨噬细胞标志)及肿瘤坏死因子(TNF)-α在滑膜组织的表达。结果CIR组与MTX+Pred组大鼠治疗2周后外周血活化的CD4+T淋巴细胞明显低于其他各组(P<0.01);4周后血清IgG、CRP水平降低,滑膜组织中CD68及TNF-α表达均明显低于单纯闻樟脑气味组、MTX+Pred减量组及空白对照组(P均<0.01)。结论以樟脑气味为条件刺激,以泼尼松和甲氨蝶呤联合免疫抑制作用为非条件刺激,通过强化训练,建立的条件免疫抑制反应可以通过调节机体的细胞免疫与体液免疫功能,抑制免疫细胞异常活化,降低自身抗体及炎性细胞因子水平,Objective To establish a conditioned immune response(CIR) for rats with collagen-induced arthritis(CIA) and investigate the immunological mechanism of CIR on CIA in rats. Methods Experimental arthritis model on healthy Wistar rats〔male,4 to 5 weeks old,(150±10) g weight〕 was reproduced by intradermal injection of Ⅱ type collagen. After that, all rats were divided into five groups randomly and treated differently:Group CIR took the smell of camphor as conditioned stimulus(CS),and MTX+Pred (methotrexate+prednisone) as unconditioned stimulus (UCS) respectively;a conditioned immune response model of rats with CIA was set up by the combination of CS and UCS for 7 times (7 days),then the rats were given CS only for another 21 days; Group MTX+Pred were treated with MTX+Pred for 4 weeks; in Group with a lower dose of MTX+Pred,rats were treated with MTX+Pred for 7 days,then treated with placebo until full of 4 weeks; in Group only smelling camphor,rats received camphor smell for 4 weeks; in Group of blank control,rats were treated with placebo for 4 weeks.Then the arthritis index was checked;flow cytometry, immunohistochemistry and turbidimetry were used to detect the expression of CD71 in peripheral blood,CD4+T cells, CD68 and tumor necrosis factor(TNF)-α in synovial tissue,and serum levels of IgG,IgM,IgA,C3,C4,C-reactive protein(CRP) of arthritic rats.Results In Group CIR and Group MTX+Pred,CD71+/CD4+ T cellcount in peripheral blood of CIA rats was much lower than that in other groups(P<0.01).The levels of IgG and CRP decreased significantly,the expression of CD68 and TNF-α in synovial tissue was much lower,compared with other groups (P<0.01).Conclusion The CIR can inhibit the inflammation of CIA by regulating the cellular and humoral immunity.

关 键 词：胶原性关节炎 条件性免疫反应 机制探讨 C反应蛋白(CRP) CD4^+T淋巴细胞 条件免疫反应 免疫组织化学检测 联合免疫抑制作用 非条件刺激 免疫散射比浊法 (TNF)-Α 肿瘤坏死因子 体液免疫功能 免疫抑制反应 细胞因子水平 

分 类 号：R593[医药卫生—内科学]