胸腺肽治疗特发性肺纤维化患者的疗效观察及机制探索

Efficacy and mechanism of thymosin in treatment of patients with idiopathic pulmonary fibrosis

目的观察胸腺肽治疗特发性肺纤维化患者的临床疗效,并探索可能的治疗机制。方法共47例特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)患者纳入研究,随机分为胸腺肽治疗组(22例)和对照组(25例),观察用药1年后两组患者的肺功能、急性加重发生率及6 min步行距离变化,并分别对治疗前后血清中细胞因子含量进行检测分析。结果与对照组相比,胸腺肽治疗组肺功能各指标变化无明显差别,但急性加重发生人数所占比例显著低于对照组(13.6%vs 40.0%,P=0.044),6 min步行距离下降值明显低于对照组[(56.64±15.42)vs(72.54±23.04)m],差异有统计学意义(P=0.009);胸腺肽治疗1年后,治疗组患者IL-1ra、INF-γ水平较对照组显著升高[(161.09±68.15)vs(72.69±24.77)pg/mL,(2.12±0.47)vs(0.96±0.44)pg/mL],差异有统计学意义(P<0.001);治疗前后组内统计分析提示,与治疗前相比,治疗组患者血清中IL-6水平在治疗后显著下降[(1.89±1.13)vs(0.61±0.36)pg/mL],差异有统计学意义(P=0.019);治疗组IL-1ra、INF-γ和IL-7水平在治疗后显著升高[(80.62±31.41)vs(161.09±68.15)pg/mL,(1.23±0.29)vs(2.12±0.47)pg/mL,(3.60±0.71)vs(5.95±1.55)pg/mL],差异有统计学意义(P值分别为0.005,0.012和0.046)。结论胸腺肽可以减少IPF患者急性加重发生率,改善患者活动耐量,并可能通过细胞因子的调节发挥抗纤维化作用。

Objective To investigate the clinical efficacy of thymosin in the treatment of idiopathic pulmonary fibrosis(IPF)and its mechanism.Methods A total of 47 patients with idiopathic pulmonary fibrosis were included in the study.They were randomly divided into thymosin treatment group(n=22)and control group(n=25).The pulmonary function,the incidence of acute exacerbation and the 6-minute walking distance of patients in the two groups were observed after one year of treatment,and the levels of cytokines in serum were detected.Results Compared with the control group,there was no significant difference in lung function decline in thymosin treatment group,but there were statistically significant differences in the incidence of acute exacerbation(13.6%vs 40.0%,P=0.044)and the decrease in 6-minute walking distance[(56.64±15.42)vs(72.54±23.04)m,P=0.009].After one year of treatment,the levels of IL-1ra and interferon INF-γin the treatment group were significantly higher than those in the control group[(161.09±68.15)vs(72.69±24.77)pg/mL,(2.12±0.47)vs(0.96±0.44)pg/mL,P<0.001].Serum levels of IL-6 decreased significantly after treatment compared with the levels before treatment[(1.89±1.13)vs(0.61±0.36)pg/mL,P=0.019].In the treatment group,levels of IL-1ra,INF-γand IL-7 were elevated after treatment[(80.62±31.41)vs(161.09±68.15)pg/mL,(1.23±0.29)vs(2.12±0.47)pg/mL,(3.60±0.71)vs(5.95±1.55)pg/mL,P=0.005,0.012 and 0.046 respectively].Conclusion Thymosin can reduce the incidence of acute exacerbations in IPF patients,improve activity tolerance in patients,and may play an anti-fibrosis role through the regulation of cytokines.