细胞因子在类风湿关节炎患者肺间质病变中的意义

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

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β1（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。

Objective To study the clinical significance of matrix metalloproteinase-9 （MMP-9）, tissue inhibitor of metalloprotenases （TIMPs） and transforming growth factor beta 1 （TGF-β1 ） 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-β1 in the serum of the three groups. Results The TIMP-1 levels of both the RA and the RA-ILD groups [ （ 645 ±220） μg/L, （ 536 ± 188 ） μg/L] were significantly higher than that of the control group [ （392 -±92） μg/L, F = 15. 221, P 〈0. 01 ]. The TGF-β1 level of the RA-ILD group [ （ 13.1 ± 10. 0） μg/L] was significantly higher than those of the control group and the RA group [ （3.9 ±2.9） μg/L, （2. 4 -± 1.7） μg/L, F =26. 455, P 〈0. 01 ]. There was no difference in the TIMP-1 level between RA-ILD and RA groups, the TGF-β1 level between the controlgroup 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） μg/L] was higher than that of the early RA-ILD group[ （420 ± 147）μg/L, t = -5. 347, P 〈0.01 ]. The TGF-β1 level in the late RA-ILD group [ （ 17.9 ±8.2） μg/ L] was higher than that of the early RA-ILD group [ （9.5 ± 9.9） μg/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） μg/L, （595 ± 110） μg/L, t = - 1.397, P=0.1743. Conclusions TGF-β1 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.