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

发布时间：2018-02-12 22:04

本文关键词： 循环纤维细胞博来霉素胶原诱导关节炎间质性肺病　出处：《细胞与分子免疫学杂志》2014年08期 　论文类型：期刊论文

【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(P0.05);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(P0.05);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,P0.01)。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。
[Abstract]:Objective to study the development of interstitial pulmonary disease induced by bleomycin (BLM) and collagen-induced arthritis combined with bleomycin induced interstitial pulmonary disease (CIA-ILD) in mice. Methods 90 C57BL / 6 mice were randomly divided into three groups: control group (control group) and CIA combined with BLM group. Observe acute inflammation of lung tissue, Sirius red staining was used to observe pulmonary fibrosis and immunohistochemical staining was used to observe the expression of 伪 -smooth muscle actin. CF(CD45 Col1 cells in peripheral blood were detected by flow cytometry. Results the pathological changes of lung tissue in both groups showed dynamic changes from alveolitis to fibrosis. Group B showed dynamic changes on the 7th and 14th day after BLM stimulation. Inflammatory lesions are most obvious. On day 21 and 28, the lesion tended to improve. In CB group, the alveolar structure was destroyed obviously with collagen deposition on the 14th day, and the lesion gradually increased to the peak on the 28th day. Compared with group B, the content of hydroxyproline in lung tissue of CB group increased significantly after 14 days. The number of CF in CB group was significantly higher than that in group B at the same time point on day 28, the immunohistochemical results showed that there were a large number of myofibroblasts in the CB group from day 14 to day 28, and the number of CF in peripheral blood and pulmonary inflammation were significantly higher in CB group than that in group B at the same time point. There was a positive correlation between the fibrosis score and the content of hydroxyproline in lung tissue. Conclusion the model of CIA-ILD mice is closer to the pathological process of RA-ILD, and the circulating fibroblasts may be involved in the pathological process of pulmonary inflammation and fibrosis.
【作者单位】：第四军医大学西京医院临床免疫科;
【基金】：国家973计划项目(2009CB521705) 国家自然科学基金(81172848)
【分类号】：R563

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