小鼠间质性肺病循环纤维细胞的水平与肺部炎症和纤维化有关  

The circulating fibrocytes are associated with the lung inflammation and fibrosis of mice with interstitial lung disease

作　　者：符亚璐 戎梦瑶[1] 朱平[1] 陈丽娜[1] 樊春梅[1] 王彦宏[1] 李嘉[1] 符向辉[1] 

机构地区：[1]第四军医大学西京医院临床免疫科,陕西西安710032

出　　处：《细胞与分子免疫学杂志》2014年第8期814-818,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家973计划项目(2009CB521705);国家自然科学基金(81172848)

摘　　要：目的 研究博来霉素（BLM）诱导的间质性肺病（ILD）和胶原蛋白诱导关节炎联合博来霉素诱导的间质性肺病（CIA-ILD）小鼠模型肺部病变的发展、病理特点及其与循环纤维细胞（CF）消长的相关性。方法 90只C57BL/6小鼠随机分为3组： 对照组（S）组、 BLM诱导（B）组和CIA联合BLM诱导（CB）组。分别于BLM处理后第2、7、14、21、28天, HE染色观察肺组织急性炎症, 天狼星红染色观察肺组织纤维化情况, 免疫组织化学染色观察α-平滑肌肌动蛋白的表达, 流式细胞术检测外周血CF（CD45＋Col1＋细胞）并与病变的程度进行相关性分析。结果 2组小鼠肺组织病理变化均呈现为肺泡炎至纤维化的动态改变, B组在BLM刺激后第7-14天炎性病变最明显, 第21、28天病变趋于好转; CB组第14天开始出现肺泡结构明显破坏伴有胶原沉积, 病变逐渐加重至第28天达最高峰; 与B组相比, CB组肺组织羟脯氨酸含量在第14天后明显增加（P〈0.05）; 2组外周血CF均在给药后出现先增高后下降的趋势, 且CB组在第14、21、28天明显高于同一时间点B组的CF数量（P〈0.05）; 免疫组化结果显示, CB组亦在第14天至第28天有大量肌纤维母细胞聚集; 外周血CF数量与肺部炎症、 纤维化评分及肺组织羟脯氨酸含量呈正相关（r=0.847、 0.826、 0.735, P〈0.01）。结论 CIA-ILD小鼠模型更为接近RA-ILD病理过程, 循环纤维细胞可能参与了肺部炎症和纤维化病理进程。Objective To study the pathological process and characteristics of bleomycin （ BLM）-induced interstitial lung disease （ILD） model and collagen-induced arthritis （CIA） complicated by BLM-induced ILD （CIA-ILD） model in mice and explore the correlations with circulating fibrocytes. Methods Ninety mice were randomly divided into normal saline group （S group）, BLM group （B group）, CIA-BLM group （CB group）, with 30 mice in each group. On the 2, ？, 14, 21 and 28 days after BLM challenge, mice of each group were sacrificed. HE staining was used to detect the degrees of acute inflammation and sirius red staining to detect lung fibrosis. Immunohistochemicstry was adopted to detect alpha-smooth muscle actin expression. The peripheral blood was obtained to count the proportion of circulating fibrocytes （CD45 ＋ COL1 ＋ ） by flow cytometry. The correlations between circulating fibrocytes and pathological changes of ILD were analyzed statistically. Results Both of the ILD model groups showed the dynamic process from pulmonary alveolitis to fibrosis gradually. Inflammatory lesion in the lungs of B group was the most obvious on the 7-14th day, and then there was a slow rehabilitation process on the 21th and 28th day. CB group began to present alveoli destruction and collagen deposition on the 14th day, and the inflammation was the most severe on the 28th day. Pulmonary hydroxyproline content was obviously ascended in CB group as compared with B group （P〈0.05） after 14 days. An increase in the total number of circulating fibrocytes was observed in both B and CB groups. It tended to increase at first, and subsequently declined. The level of circulating fibrocytes was higher in CB group than in B group on day 14, 21 and 28 （P 〈0.0,5）. The immunohistochemical results showed that there were many myofibroblasts infiltrating in CB group from the 14th day to 28th day. The number of circulating fibrocytes in peripheral blood was positively correlated with pulmonary inflammation, fibrosis de

关 键 词：循环纤维细胞 博来霉素 胶原诱导关节炎 间质性肺病 

分 类 号：R392.33[医药卫生—免疫学] R563[医药卫生—基础医学]