依那西普抑制类风湿性关节炎滑膜炎症并降低黏附相关分子表达  

Etanercept inhibits synovial inflammation and reduces the expression of adhesion related molecules in synovial tissues of patients with rheumatoid arthritis

作　　者：曹争明[1] 丁孝权[1] 黄越龙[1] 刘松洋[1] 林剑浩[1] 吕厚山[1] 孙铁铮[1] 

机构地区：[1]北京大学人民医院关节病诊疗研究中心,北京100044

出　　处：《细胞与分子免疫学杂志》2015年第4期511-515,519,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金青年基金(30801160)

摘　　要：目的观察肿瘤坏死因子(TNF)拮抗剂依那西普治疗的类风湿性关节炎(RA)患者滑膜组织炎症评分及相关分子标志物表达的改变。方法行膝关节镜下滑膜切除术治疗的RA患者16例,其中8例既往接受依那西普治疗,8例未接受依那西普或其他生物制剂治疗。滑膜组织HE染色比较2组患者Rooney炎症评分,免疫组织化学染色检测滑膜组织中增殖细胞核抗原(PCNA)及血管黏附分子1(VCAM-1)、细胞间黏附分子1(ICAM-1)和钙黏素11(cadherin-11)的表达。结果依那西普组Rooney评分明显低于非生物制剂组,滑膜衬里层PCNA与cadherin-11表达明显降低,衬里下层PCNA及cadherin-11表达也显著降低。两组间滑膜衬里层及衬里下层VCAM-1与ICAM-1表达无显著性差异。临床炎性指标[红细胞沉降率(ESR)、C反应蛋白(CRP)、血小板计数(PLT)]及28个关节疾病活动指数(DAS28)与Rooney评分之间无统计学相关性。结论依那西普可抑制RA滑膜细胞增生和淋巴细胞浸润,并降低与增生及黏附相关分子的表达,缓解RA滑膜组织炎性病变;临床炎性指标不能完全反映局部关节滑膜组织学改变。Objective To observe the changes of synovial inflammation score and expression of related molecular markers in patients with rheumatoid arthritis treated with tumor necrosis factor（TNF） antagonist etanercept.Methods Sixteen patients with rheumatoid arthritis received synovectomy in the knee under arthroscopy,of which 8 patients had been treated with etanercept before surgery（etanercept group） and the other 8 patients were given no etanercept or other biologics（non-biological agent group）.The synovial tissues obtained from surgery were subjected to HE staining and immunohistochemical staining respectively,to assess Rooney＇s inflammation score and detect the expressions of proliferating cel nuclear antigen（PCNA）,vascular cel adhesion molecule-1（VCAM-1）,intercel ular adhesion molecule-1（ICAM-1） and cadherin-11.Results Rooney＇s score in etanercept group was significantly lower than that in non-biological agent group.The expressions of PCNA and cadherin-11 in synovial lining and sublining layers significantly decreased in etanercept group.Expressions of VCAM-1 and ICAM-1had no significant difference in either synovial lining or sublining layer between the two groups.Clinical inflammatory markers including erythrocyte sedimentation rate（ESR）,C-reactive protein（CRP）,platelet count（PLT） and disease activity score in 28 joints（DAS28） had no statistical correlation with Rooney＇s inflammation score.Conclusion Etanercept could effectively inhibit proliferation of synoviocytes and infiltration of lymphocytes in synovium of rheumatoid arthritis,and decrease the expressions of proliferation-and adhesion-related molecular markers,which histologically alleviated the synovial inflammation of rheumatoid arthritis.Clinical inflammatory markers might not fully reflect histological changes in the local synovial tissue.

关 键 词：TNF拮抗剂 依那西普 类风湿性关节炎 滑膜炎 

分 类 号：R392.5[医药卫生—免疫学] R593.22[医药卫生—基础医学]