咯利普兰对类风湿关节炎合并间质性肺疾病患者外周血单个核细胞核因子-κB、肿瘤坏死因子α、白细胞介素-8表达的影响  

Effect of selective phosphodiesterase 4 inhibitors on nuclear factor kappa B, tumor necrosis factor-α and interleukin-8 expression in peripheral blood mononuclear cells in rheumatoid arthritis with interstitial lung disease

作　　者：宋宁[1] 刘爱京[2] 高雪峰 郭宪立[4] 关继涛[1] 吴建玲[1] 张瑞芳[1] 段林[1] 贺文舒[1] 

机构地区：[1]河北医科大学第二医院呼吸内科,石家庄050000 [2]河北医科大学第二医院免疫风湿科,石家庄050000 [3]河北省正定县人民医院内科 [4]河北医科大学第二医院急诊科,石家庄050000

出　　处：《中华内科杂志》2013年第10期829-832,共4页Chinese Journal of Internal Medicine

基　　金：河北省科技厅科技支撑计划（10276105D-50）;河北省卫生厅《河北省2011年医学科学重点项目计划》（20110334）

摘　　要：目的 探讨选择性磷酸二酯酶4（PDE4）抑制剂对类风湿关节炎（RA）合并间质性肺疾病（ILD）患者外周血单个核细胞（PBMC）体外产生促炎性细胞因子的影响及机制,为选择性PDE4抑制剂治疗RA合并ILD提供理论依据.方法 采集15例健康志愿者（健康对照组）和20例初治活动期RA合并ILD患者（RA合并ILD组）的PBMC.RA合并ILD组PBMC分为空白对照组、茶碱组、咯利普兰组和地塞米松组,免疫细胞化学法检测PBMC核因子-κB （NF-κB） p65阳性细胞百分率,酶联免疫吸附测定法（ELISA）检测PBMC培养上清中肿瘤坏死因子α（TNFα）、白细胞介素-8（IL-8）水平.结果 （1）健康对照组、RA合并ILD组中咯利普兰组、地塞米松组PBMC培养上清中TNFα、IL-8水平和NF-κB p65阳性细胞百分率低于空白对照组（P＜0.01）,咯利普兰组、地塞米松组低于茶碱组（P＜0.01）；地塞米松组IL-8水平低于咯利普兰组（P＜0.05）.（2）相关性分析：RA合并ILD组PBMC培养上清中NF-κB p65阳性细胞百分率与TNFα、IL-8水平呈正相关（r值分别为0.902、0.735,P＜0.01）.咯利普兰组NF-κBp65阳性细胞百分率与TNFα、IL-8水平呈正相关（r=0.874,P＜0.01;r =0.561,P ＜0.05）.结论 RA合并ILD患者PBMC NF-κB活化并产生促炎性细胞因子,参与了RA合并ILD的发病过程；选择性PDE4抑制剂可能通过抑制NF-κB活性抑制PBMC产生促炎性细胞因子,从而抑制RA合并ILD的炎症反应.Objective To investigate the effect of selective phosphodiesterase （PDE） 4 inhibitors on nuclear factor kappa B （ NF-KB）, tumor necrosis factor-α （TNFα） and interleukin-8 （ IL-8 ） secreted by peripheral blood mononuclear cells （PBMCs） in patients diagnosed as rheumatoid arthritis with interstitial lung disease （RA-ILD）. Methods PBMCs isolated from 15 healthy volunteers （group A） and 20 patients with untreated active RA-ILD （group B ） were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment ： blank group （ B1 ）, theophylline group （ B2 ） , selective PDE4 inhibitor rolipram group （ B3 ） , and glucocorticoid group （IM） with dexamethasone. The expression of NF-KB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay （ELISA）. Results （ 1 ） The activity of NF-KB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A （P 〈 O. 01 ）. Compared with group B1, three parameters above were similar to those in group B2 （ P 〉 O. 05 ）, while group B3 and group B4 had significant decreased levels of three parameters （P 〈 O. Ol ） ; IL-8 level in group B4 was significantly lower than that in group B3 （P 〈 O. 05 ）. （2）TNFc~ and IL-8 levels were positively correlated with NF-KB activity in group B （ r = O. 902 and 0. 735, P 〈 O. O1 respectively）. （3） The reduction of TNFc~ and IL-8 levels were positively correlated with reduction of NF-KB activity after intervention of rolipram in group B3 （ r = 0. 874, P 〈 O. O1 ; r = O. 561, P 〈 0. 05 respectively ） . Conclusion NF-KB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDFA inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor

关 键 词：关节炎 类风湿 肺疾病 间质性 咯利普兰 肿瘤坏死因子Α 白细胞介素8 NF-κB 

分 类 号：R593.22[医药卫生—内科学]