咯利普兰抑制类风湿关节炎间质性肺疾病患者外周血单个核细胞体外增殖

ROLIPRAM INHIBITS ACTIVITY OF PROLIFERATION IN PERIPHERAL BLOOD MONONUCLEAR CELLS FROM RHEUMATOID ARTHRITIS PATIENTS WITH INTERSTITIAL LUNG DISEASE AND ITS MECHANISM

目的探讨选择性磷酸二酯酶(phosphodiesterase,PDE)4抑制剂咯利普兰对类风湿关节炎间质性肺疾病(rheumatoid arthritis-interstitial lung disease,RA-ILD)患者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)体外增殖的影响及机制,为选择性PDE4抑制剂治疗RA-ILD提供理论依据。方法采集20例初治活动期RA-ILD患者的PBMC,采用四甲基偶氮唑盐(methyl thiazolyl blue tetrazolium bromide,MTT)比色法检测RA-ILD患者不同浓度咯利普兰处理的PBMC的增殖活性,采用免疫细胞化学法检测核因子κB(nuclear factor-κB,NF-κB)p65核染色阳性细胞百分率。结果咯利普兰剂量依赖性抑制RA-ILD患者PBMC的增殖活性,并降低NF-κB p65核染色阳性细胞百分率(P<0.01)。结论咯利普兰可能通过抑制NF-κB活化抑制RA-ILD患者PBMC的增殖活性,具有治疗RA-ILD的潜能。

Objective To investigate the effect of selective phosphodiesterase （PDE） 4 inhibitor rolipram on aetivity of proliferation in peripheral blood mononuclear cells （PBMC） from rheumatoid arthritis patients with interstitial lung disease （RA-ILD） and its mechanism. Methods PBMC isolated from 20 patients with untreated active RA-ILD were cultured in vitro. The activity of proliferation in PBMC was detected by methyl thiazolyl blue tetrazolium bromide （MTY） spectrophotometry and the expression of nuclear factor （NF）-KB was determined by immunocytochemical staining. Results Rolipram inhibited PBMC proliferation activity, and reduced NF-KB p65 nuclear staining positive percentage in a dose-dependent manner（P 〈 0.01 ）. Conclusion Rolipram may inhibit the proliferation activity of PBMC through the inhibition of NF-KB activation in RA-ILD patients, which suggests that selective PDE 4 inhibitors have a potential for the treatment of RA-ILD.