Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transpl Immunol. 2013 Jun;28(4):170-5. doi: 10.1016/j.trim.2013.04.006. Epub 2013 Apr 22.
Several animal models have been established to investigate the mechanisms of obliterative bronchiolitis after lung transplantation. In this study, we compared three prevalent murine models of obliterative bronchiolitis in terms of several basic pathologic changes in a relatively short span of time after transplantation.
Each of the recipient mice simultaneously received orthotopic, intra-omental and subcutaneous tracheal transplantation in both syngeneic and allogeneic settings. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day 14, 21 and 28 after transplantation for histological and immunohistochemical analyses.
Syngeneic tracheal grafts from different transplant sites retained normal histologic structures, while their corresponding allografts demonstrated more occlusion of the airway lumen as well as more infiltration of CD4(+)/CD8(+) mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with two heterotopic allografts, orthotopic allografts had less occlusion of the tracheal lumen as well as less infiltration of CD4(+)/CD8(+) mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized vessels (P<0.05).
Orthotopic tracheal transplantation in mice can be considered as a model to study early stages of obliterative bronchiolitis, and heterotopic tracheal transplantation can be a model for late stages of obliterative bronchiolitis.
已经建立了几种动物模型来研究肺移植后闭塞性细支气管炎的机制。在这项研究中,我们比较了三种常见的闭塞性细支气管炎小鼠模型,比较了它们在移植后相对较短的时间内的几种基本病理变化。
受体小鼠同时接受同种和同种异体原位、腹腔内和皮下气管移植。不给予免疫抑制治疗。在移植后第 14、21 和 28 天采集气管移植物进行组织学和免疫组织化学分析。
来自不同移植部位的同种气管移植物保留了正常的组织学结构,而相应的同种异体移植物表现出更多的气道腔闭塞以及更多的 CD4+/CD8+单核细胞和肌成纤维细胞浸润,但在指定时间内再生上皮和新生血管化的血管较少(P<0.05)。与两个异位同种异体移植物相比,原位同种异体移植物的气管腔闭塞较少,CD4+/CD8+单核细胞和肌成纤维细胞浸润较少,但再生上皮和新生血管化的血管较多(P<0.05)。
在小鼠中进行的原位气管移植可被视为研究闭塞性细支气管炎早期阶段的模型,而异位气管移植可作为闭塞性细支气管炎晚期阶段的模型。