IL-22在类风湿关节炎相关间质性肺病中的表达及其意义  

Expression and function of IL-22 in rheumatoid arthritis-associated interstitial lung disease

作　　者：方权权 屈梓叶 谢京志 宗娟 周冬梅 殷松楼 殷寒秋 FANG Quanquan;QU Ziye;XIE Jingzhi;ZONG Juan;ZHOU Dongmei;YIN Songlou;YIN Hanqiu(Department of Rheumatology and Immunology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221004,China)

机构地区：[1]徐州医科大学附属医院风湿免疫科,江苏徐州221004

出　　处：《中华全科医学》2024年第6期951-956,1004,共7页Chinese Journal of General Practice

基　　金：江苏省研究生实践创新项目(SJCX22_1274);徐州市科技计划项目(KC21157)。

摘　　要：目的观察IL-22在类风湿关节炎相关间质性肺病中(RA-ILD)的表达情况,建立动物模型探讨IL-22在肺纤维化中的作用。方法选择2021年10月—2022年10月在徐州医科大学附属医院初诊初治的类风湿关节炎合并(RA-ILD组)/未合并(RA-NILD组)间质性肺病患者各33例,同期14位健康体检者为健康对照组,采用ELISA测定3组外周血IL-22水平并比较。采用Pearson检验分析IL-22水平与肺HRCT评分的相关性;采用多因素logistic回归分析研究RA-ILD的危险因素并绘制ROC曲线。生理盐水(NS)和博来霉素(BLM)处理野生小鼠(WT)与IL-22敲基因小鼠(IL-22KO),建模后予腹腔注射IL-22,HE和Masson染色观察肺组织病理改变,RT-qPCR、Western blotting检测纤维化标志物水平。结果RA-NILD组IL-22水平高于RA-ILD组及健康对照组,其水平与HRCT评分呈负相关关系(r=-0.940,P<0.05)。Logistic回归分析提示IL-22水平是RA-ILD的影响因素,IL-22联合年龄、吸烟、APCA、MCHC诊断RA-ILD的AUC为0.959(95%CI:0.916~1.000),灵敏度为97.0%,特异度为87.9%。病理染色示BLM组小鼠肺部胶原面积较NS组增多,Szapiel’s评分和Ashcroft评分升高,纤维化相关基因(CollagenⅠ、Vimentin、α-SMA)的mRNA和蛋白质表达也较NS组增高,其中IL-22KO组较WT组增高更显著(P<0.05)。IL-22治疗后胶原沉积及纤维化基因的mRNA和蛋白表达明显减少(P<0.05)。结论IL-22可能对肺纤维化具有保护作用,未来可能成为潜在的治疗靶点,并可用于临床预测RA-ILD。Objective This study aims to observe the expression of IL-22 in patients with rheumatoid arthritis-associated interstitial lung disease(RA-ILD)and establish an experimental model to explore its role in pulmonary fibrosis.Methods We selected 33 patients with rheumatoid arthritis with or without interstitial lung disease,who were newly diagnosed and treated at the Affiliated Hospital of Xuzhou Medical University from October 2021 to October 2022.Additionally,14 healthy subjects were chosen as controls during the same period.ELISA was used to detect the peripheral blood IL-22 levels in the three groups,and a comparison was made among them.Spearman correlation test was employed to analyze the correlation between IL-22 and lung HRCT scores.Logistic regression was used to analyze risk factors for RA-ILD and to draw ROC curves.Wild mice(WT)and IL-22 knock-out mice(IL-22KO)were treated with normal saline(NS)and Bleomycin(BLM).Following modeling,mice were given intraperitoneal injections of IL-22.HE and Masson staining were used to observe the histopathological changes in the lung tissues.Relevant markers were detected by RT-qPCR and Western blotting.Results The levels of IL-22 were higher in the RA-NILD group compared to the RA-ILD group and the healthy control group.There was a negative correlation between IL-22 levels and lung HRCT scores(r=-0.940,P<0.05).Logistic regression analysis suggested that a low level of IL-22 was an independent risk factor for RA-ILD.The combined diagnosis of RA-ILD with IL-22,age,smoking,APCA,and MCHC had an AUC of 0.959(95%CI:0.916-1.000),with a sensitivity of 97.0%and specificity of 87.9%.HE and Masson staining found that the collagen deposition in the lungs of BLM groups were increased compared with the NS groups,accompanied by Szapiel's scores and Ashcroft scores.The mRNA and protein expression of fibrosis-related genes(CollagenⅠ,Vimentin,andα-SMA)were increased in the BLM groups compared to the NS group,and the IL-22KO group showed even higher levels(P<0.05).Treatment with IL-22 resu

关 键 词：类风湿关节炎相关间质性肺病 间质性肺病 白介素-22 

分 类 号：R593.21[医药卫生—内科学] R563[医药卫生—临床医学]