A model of chronic lung allograft rejection in the rat
A model of chronic lung allograft rejection in the rat
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DOI：
10.1183/09031936.00110609
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发表时间：
2010-06-01
影响因子：
24.3
通讯作者：
Weder, W.
中科院分区：
文献类型：
--
作者：
Jungraithmayr, W.;Vogt, P.;Weder, W.
闭塞性细支气管炎是慢性肺排斥反应的病理标志，严重影响肺移植后的长期生存。然而，这种病理生理学现象的实验再现还没有实现与当代体内模型。本文描述了一种慢性排斥反应模型，致敏受体接受单侧原位大鼠肺移植，在第21-84天分析了刘易斯大鼠，在接受来自刘易斯x棕色挪威F（1）杂交供体的左肺移植前7天，用棕色挪威大鼠的皮肤致敏。慢性排斥反应的发展是由雷帕霉素和环孢霉素的治疗调制，其特征在于组织学，免疫化学和逆转录酶PCR.Characteristic组织病理学变化，导致慢性排斥反应诱导随着时间的推移，在持续的雷帕霉素应用的存在下与环孢霉素的初始治疗。在第84天，纤维化病变取代了小细支气管内的呼吸上皮，具有平滑肌α-肌动蛋白的强表达和T辅助细胞1型细胞因子、平滑肌α-肌动蛋白、转化生长因子β和CC趋化因子配体5的mRNA的上调，但减少叉头盒蛋白P3基因表达。一个可重复的和临床相关的实验组-在大鼠肺同种异体移植物中进行性慢性排斥反应。该模型将允许更好地了解闭塞性细支气管炎发展过程中小气道的病理变化，并可作为测试新的治疗干预措施的疗效的体内设置。
Bronchiolitis obliterans, the pathological hallmark of chronic pulmonary rejection, severely impacts long-term survival following lung transplantation. However, experimental reproduction of this pathophysiological phenomenon has not been achieved with contemporary in vivo models. Here, a model of chronic rejection is described, with sensitised recipients receiving unilateral orthotopic rat lung transplants.Lewis rats, sensitised with skin from brown Norway rats 7 days before receiving left lung transplants from donors that were Lewis x brown Norway F(1) hybrids, were analysed during day 21-84. The development of chronic rejection was modulated by a treatment with rapamycin and cyclosporin, and characterised histologically, immunohistochemically and by reverse transcriptase PCR.Characteristic histopathological changes leading to chronic rejection were induced over time by an initial treatment with cyclosporin in the presence of continuous rapamycin application. At day 84, fibrotic lesions replaced the respiratory epithelium within small bronchioles, with strong expression of smooth muscle alpha-actin and upregulation of mRNA for T-helper cell type-1 cytokines, smooth muscle alpha-actin, transforming growth factor-beta and CC chemokine ligand 5, but decreased forkhead box protein P3 gene expression.A reproducible and clinically relevant experimental set-up for progressive chronic rejection in rat pulmonary allografts is described. This model will permit better understanding of the pathological changes of small airways during the development of bronchiolitis obliterans, and may serve as an in vivo set-up for testing the efficacy of novel therapeutic interventions.