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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 development of pulmonary lesions induced by bleomycin (BLM) -induced interstitial lung disease (ILD) and collagen-induced arthritis combined with bleomycin-induced interstitial lung disease (CIA-ILD) Characteristics and its relationship with the decline of circulating fibroblasts (CF). Methods Ninety C57BL / 6 mice were randomly divided into 3 groups: control group (S), BLM induction (B) group and CIA combined with BLM induction (CB) group. At 2, 7, 14, 21 and 28 days after BLM treatment, acute inflammation of lung tissue was observed by HE staining. Lung fibrosis was observed by Sirius red staining. The expression of α-smooth muscle actin was observed by immunohistochemical staining Peripheral blood CF (CD45 + Col1 + cells) were detected by cytometry and correlated with the degree of lesion. Results The histopathological changes of lung tissue in both groups showed dynamic change from alveolitis to fibrosis. In group B, the inflammatory lesions were the most obvious on the 7th to 14th days after BLM stimulation, and the lesions on the 21th and 28th days tended to improve. In the CB group Compared with B group, the content of hydroxyproline in lung tissue of CB group increased significantly on the 14th day (P <0.05), compared with the B group ). CF in both groups increased first and then decreased after administration, and the number of CF in group CB was significantly higher than that in group B (P <0.05) on the 14th, 21st and 28th day The results also showed that there were a large number of myofibroblasts in CB group from the 14th day to the 28th day. The number of peripheral blood CF was positively correlated with lung inflammation, fibrosis score and hydroxyproline content in lung tissue (r = 0.847,0.826 , 0.735, P <0.01). Conclusion CIA-ILD mouse model is more close to the pathological process of RA-ILD, and circulating fibroblasts may be involved in the pathological process of lung inflammation and fibrosis.