沙利度胺联合强的松治疗特发性肺间质纤维化的疗效及相关细胞因子研究

Clinical research and correlated cytokine study of thalidomide combined with prednisone on idiopathic pulmonary fibrosis

目的探讨沙利度胺联合强的松治疗特发性肺间质纤维化(IPF)的临床疗效;肿瘤坏死因子α(TNF-α)、转化生长因子β(TGF-β)在IPF发病中的作用;沙利度胺对IPF患者TNF-α及TGF-β的影响。方法 IPF患者57例,20例单用强的松治疗(激素组),37例应用沙利度胺联合强的松治疗(联合治疗组),3个月后进行疗效判定;用酶联免疫法(ELISA)分别检测两组患者治疗前后肺泡灌洗液(BALF)及血清中TNF-α、TGF-β1的变化,同时检测20例健康志愿者(对照组)BALF液及血清中TNF-α、TGF-β1,作为对照组。结果联合治疗组临床总有效率高于激素组(P<0.05);IPF患者的BALF液及血清中TNF-α、TGF-β1均明显高于对照组(P<0.01),治疗后,激素组及联合治疗组BALF液及血清中TNF-α、TGF-β1均较治疗前下降(P<0.05),联合治疗组BALF液及血清中TNF-α、TGF-β1下降幅度明显高于激素组(P<0.01)。结论沙利度胺联合强的松可有效控制IPF发展;TNF-α、TGF-β1在IPF发病中起重要作用,沙利度胺联合强的松对其抑制作用更强;沙利度胺通过降低TNF-α、TGF-β1表达来抑制肺纤维化。

Objective To investigate the therapeutic effect of thalidomide combined with prednisone on idiopathic pulmonary fibrosis（IPF）,explore the role of tumor necrosis factor α（TNF-α）and transforming growth factor β（TGF-β）in pathogenesis of IPF,and observe the influence of thalidomide on TNF-α and TGF-β1 in patients with IPF.Methods 57 IPF patients were randomly divided into hormone group（n=20,prednisone）and treatment group（n=37,prednisone combined with thalidomine）.The curative effect,bronchoalveolar lavage fluid（BALF）and serum levels of TNF-α and TGF-β1 inpatients with IPF were detected by ELISA before and after 3-month treatment,meanwhile,the BALF and serum in health volunteer（n=20）were detected as control.Results The total effective rate of treatment group was higher than that of hormone group（P0.05）;the BALF and the serum levels of TNF-α and TGF-β1 in patients with IPF were significantly higher than those of control group（P0.01）,those in hormone group and treatment group both decreased after treatment（P0.01）,and the decrease in treatment group were higher than those in hormone group（P0.01）.Conclusion Thalidomide combined with prednisone can prevent pulmonary interstitial fibrosis;TNF-α and TGF-β1 play an important role on pathogenesis of IPF;thalidomide can inhibit the pulmonary fibrosis through lowering the levels of TNF-α and TGF-β1.