摘要目的 通过观察膝骨关节炎(knee osteoarthritis,KOA)患者肺功能参数、B、T淋巴细胞衰减因子(B and T lymphocyte attenuator,BTLA)及血清细胞因子的变化情况,探讨KOA患者肺功能变化的可能分子机制.方法 选取2011年10月-2012年7月安徽中医学院第一附属医院风湿病科收治的住院、门诊患者47例.应用肺功能仪检测患者肺功能指标；流式细胞术检测BTLA；ELISA法检测白介素(interleukin,IL)-1β、IL-10、基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶组织抑制物-1(tissue inhibitor of matrix metalloprotease-1,TIMP-1)；魏氏法测定血沉(erythrocyte sedimentation rate,ESR)；日立7060型全自动生化分析仪进行测定超敏C反应蛋白(high-sensitivityC-reactive protein,hs-CRP).结果 (1)与正常组比较,KOA患者用力肺活量(forced vital capacity,FVC)、一秒用力呼气容积(forced expiratory volume in 1 second,FEV1)、FEV1/FVC、用力最大呼气流量(peak expiratory flow,PEF)、最大呼气中段流量(maximal mid-expiratory flow,MEF25-75)、用力呼气50％流量(Maximal mid-expiratory flow velocity in pulmonary vital capacity 50％,MEF50)、用力呼气25％流量(maximal mid-expiratory flow velocity in pulmonary vital capacity 25％,MEF25)、CD3+ BTLA+T细胞、CD4+BTLA+T细胞、IL-10、TIMP1明显降低,IL-1β、MMP9明显升高.(2)相关性分析显示,FVC与Lequesne MG、症状分级量化总分、病程、MMP9呈负相关,与CD3+ BTLA+T细胞、IL-10、TIMP1呈正相关；FEV1与CD3+ BTLA+T细胞、CD4+BTLA+T细胞、TIMP1呈正相关,与病程呈负相关；MEF50与CD3+ BTLA+T细胞、CD4+ BTLA+T细胞呈正相关.结论 KOA患者在发生关节软骨病变的同时,伴有肺功能的下降.其机制可能与BTLA表达水平下降,IL-1β、MMP9明显升高,IL-10、TIMP1明显降低,诱发异常免疫应答,从而介导气道损伤,导致KOA患者肺功能下降有关.

abstractsObjective To observe the changes of lung parameters,the ratios of B and T lymphocyte attenuator(BTLA) and serum cytokines in patients with knee osteoarthritis (KOA),and explore possible molecular mechanism of them.Methods Forty-seven cases of knee osteoarthritis from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from 2011 October to 2012 July were analyzed in this study.Pulmonary parameters were detected by spirometer; B and T lymphocyte attenuator(BTLA) was detected by flow cytometry ; Interleukin (IL)-1β,IL-10,matrix metalloproteinase-9 (MMP-9),tissue inhibitor of matrix metalloprotease-1 (TIMP-1) were detected by ELISA;ESR was determined by Westergren method ; hs-CRP was determined by the automatic biochemistry analyzer.Results (1) Compared with NC group,levels of FVC,FEV1,FEV1/FVC,PEF,MEF25.75,MEF50,MEF25,CD3 + BTLA+ T cell,CD4+ BTLA+ Tcell,IL-10,TIMP1 were significantly decreased,IL-1 β,MMP9 were significantly increased.(2)Correlation analysis showed FVC was negatively correlated to Lequesne MG,symptom classify quantization scores,course,MMP9,while positively related to CD3+ BTLA+T cell,IL-10,TIMP1 ;FEV1 was positively correlated to CD3 + BTLA+T cell,CD4+ BTLA+T cell,TIMP1,while negatively correlated to course ; MEF50 was positively related to CD3+BTLA+T cell,CD4+ BTLA+T cell.Conclusion While articular cartilage lesions occurred in KOA patients,the lung function was also declined.The mechanism may be associated with the declination of expression of BTLA,which can cause up-regulating of IL-1 β,MMP9 and down-regulating of IL-10,TIMP1,thus leading to immune dysfunction and abnormal immune response.Those may induce airway injuries and result in lung function decline finally.