硬皮病伴发肺间质病变小鼠模型的建立及发病机制研究

发布时间：2018-04-16 11:24

本文选题：硬皮病 + 肺间质病变　；参考：《复旦学报(医学版)》2015年04期

【摘要】：目的建立硬皮病伴发肺间质病变(systemic scleroderma associated with interstitial lung disease,SscILD)的小鼠动物模型,并初步探讨其发病机制。方法造模组以0.4 mg/mL浓度博来霉素(bleomycin,BLM)背部中央区域局部皮下注射0.1 mL/天,连续28天;对照组以PBS缓冲液(pH=7.4)相同方法处理;连续观察2组小鼠大体形态变化,以HE和Masson染色明确模型的可靠性,通过检测羟脯氨酸了解纤维化程度,并通过免疫组化检测TGF-β1、α-SMA、collagen-1、MMP-9、CD8+T细胞、CD68+巨噬细胞、IL-23的表述。结果造模组小鼠皮肤显著硬化,镜下真皮层显著增厚,胶原纤维束增多,排列紧密,胶原含量升高,符合硬皮病表现;并且肺组织出现明显炎症和纤维化,胶原含量显著升高,免疫组化检测发现TGF-β1、collagen-1、MMP-9、α-SMA、CD8+T细胞、CD68+巨噬细胞、IL-23的表达均显著性增高(P均0.05)。结论 C3H/He小鼠连续28天皮下注射0.4 mg/mL的BLM能诱导Ssc-ILD动物模型,出现符合Ssc标准的皮肤改变,肺部出现明显的炎症和纤维化,与TGF-β1升高密切相关,并伴随α-SMA、collagen-1、MMP-9、CD8+T细胞、CD68+巨噬细胞、IL-23增多。
[Abstract]:Objective to establish a murine model of systemic scleroderma associated with interstitial lung disease (SSCILD) of scleroderma with pulmonary interstitial disease, and to explore the pathogenesis of Scleroderma.Methods the model group was treated with 0.4 mg/mL bleomycin bleomycin (BLM) for 28 days subcutaneously, and the control group was treated with PBS buffer solution (pH = 7.4). The gross morphologic changes of the two groups were observed continuously.According to the reliability of HE and Masson staining, the degree of fibrosis was determined by detecting hydroxyproline, and the expression of IL-23 on CD68 macrophages was detected by immunohistochemical staining of TGF- 尾 _ 1, 伪 -SMA-collagen-1MMP-9 / CD8 T cells.Results the skin of the model group was significantly sclerotic, the dermis of the model group was significantly thickened under microscope, the collagenous bundles were increased, the collagenous fibers were arranged closely, the collagen content was increased, which was consistent with the manifestation of scleroderma, and there was obvious inflammation and fibrosis in the lung tissue, and the collagen content increased significantly.The expression of IL-23 in CD68 macrophages of TGF- 尾 1 collagen-1 and 伪 -SMA-CD8 T cells were all significantly increased by immunohistochemistry (P < 0.05).Conclusion the model of Ssc-ILD could be induced by subcutaneously injection of 0.4 mg/mL BLM for 28 days in C3H/He mice, and the skin changes in accordance with the Ssc standard, the obvious inflammation and fibrosis in the lungs, were closely related to the increase of TGF- 尾 _ 1.In addition, the number of IL-23 in CD68 macrophages was increased with 伪 -SMA-collagen-1 MMP-9 and CD8 T cells.
【作者单位】：复旦大学附属中山医院皮肤科;复旦大学附属中山医院实验研究中心;复旦大学附属中山医院病理科;
【分类号】：R593.25;R-332

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