细胞因子在类风湿关节炎患者肺间质病变中的意义

目的 探讨类风湿关节炎(RA)继发间质性肺疾病(RA-ILD)患者血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子(TIMP-1)和转化生长因子β,(TGF-β1)的变化及其意义.方法 RA组29例,RA-ILD组28例(其中早期RA-ILD组16例,中晚期RA-ILD组12例),对照组为健康体检人员29名.采用ELASA法检测血清中MMP-9、TIMP-1和TGF-β1水平.计量资料用-x±s表示,多组间比较采用方差分析,两组间比较采用t检验,关节分级资料采用卡方检验.结果 RA组和RA-ILD组血清TIMP-1水平[(645±220)和(536±188)μg/L]明显高于对照组[(392±92)μg/L],RA-ILD组血清TGF-β1.水平[(13.1±10.0)μg/L]明显高于RA组和对照组[(3.9±2.9)和(2.4±1.7)μg/L],RA组与RA-ILD组血清TIMP-1水平、RA组与对照组血清TGF-β1的水平无明显差别.各组血清MMP-9水平和MMP-9/TIMP-1均无明显差别.中晚期RA-ILD组血清TIMP-1水平[(690±110)μg/L]明显高于早期RA-ILD组[(420±147)μg/L],中晚期RA-ILD组血清TGF-β1水平[(17.9±8.2)μg/L]明显高于早期RA-ILD组[(9.5±9.9)μg/L].中晚期RA-ILD组血清MMP-9/TIMP-1(0.9±0.1)明显低于早期RA-ILD组(1.2±0.4).早期RA-ILD组血清MMP-9水平[(537±309)μg/L]与中晚期RA-ILD组[(595±110)μg/L]无明显差别.结论 血清TGF-β1可以作为RA患者ILD的诊断标志,且在一定程度上可反映RA-ILD肺部病变的严重程度.MMP-9/TIMP-1下降能反映肺部病变的严重程度.血清MMP-9水平不能作为RA-ILD的诊断指标及ILD肺部病变严重程度的判定指标.

The serum levels of cytokines in patients with rheumatoid arthritis associated interstitial lung disease and their clinical significance

OBJECTIVE: To study the clinical significance of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloprotenases (TIMPs) and transforming growth factor beta 1 (TGF-beta1) in the serum of patients with rheumatoid arthritis (RA) associated interstitial lung disease (ILD). METHODS: Twenty-nine patients with RA only (the RA group) and 28 patients with RA associated ILD (the RA-ILD group) were included in the study. Patients in the RA-ILD group were divided into 2 subgroups, 16 in the early RA-ILD group and 12 in the late RA-ILD group. Twenty-nine healthy volunteers served as the control group. ELISA was used to detect the levels of MMP-9, TIMP-1, TGF-beta1 in the serum of the three groups. RESULTS: The TIMP-1 levels of both the RA and the RA-ILD groups [(645 +/- 220) microg/L, (536 +/- 188) microg/L] were significantly higher than that of the control group [(392 +/- 92) microg/L, F = 15.221, P < 0.01]. The TGF-beta1 level of the RA-ILD group [(13.1 +/- 10.0) microg/L] was significantly higher than those of the control group and the RA group [(3.9 +/- 2.9) microg/L, (2.4 +/- 1.7) microg/L, F = 26.455, P < 0.01]. There was no difference in the TIMP-1 level between RA-ILD and RA groups, the TGF-beta1 level between the control group and the RA group, the MMP-9 level and MMP-9/TIMP-1 ratio among the three groups. The TIMP-1 level in the late RA-ILD group [(690 +/- 110) microg/L] was higher than that of the early RA-ILD group [(420 +/- 147) microg/L, t = -5.347, P < 0.01]. The TGF-beta1 level in the late RA-ILD group [(17.9 +/- 8.2) microg/L] was higher than that of the early RA-ILD group [(9.5 +/- 9.9) microg/L, t = - 2.39, P < 0.05]. The MMP-9/TIMP-1 ratio of the late RA-ILD group (0.9 +/- 0.1) was lower than that of the early RA-ILD group (1.2 +/- 0.4, z = 4.307, P < 0.01). There was no statistic significance in the MMP-9 level between the early and the late RA-ILD groups [(537 +/- 309) microg/L, (595 +/- 110) microg/L, t = - 1.397, P = 0.174]. CONCLUSIONS: TGF-beta1, can be used as a diagnostic marker of ILD in RA patients and it also reflects the pathological change of the lung. The decrease of MMP-9/TIMP-1 ratio in RA patients with ILD can reflect the severity degree of lung pathological changes.