Xu Haichao, Abuduwufuer Abudumailamu, Lv Wang, Zhou Zhenyu, Yang Yunhai, Zhang Chong, Hu Jian
Thoracic Surgery, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, China.
J Cardiothorac Surg. 2019 Jan 29;14(1):27. doi: 10.1186/s13019-019-0832-z.
Graft function may be affected if the organ is exposed to hypoxia. We hypothesized that bronchiolitis obliterans (BO) after lung transplantation is associated with hypoxia-inducible factor-1α (HIF-1α). This study compares the expression of HIF-1α and its downstream proteins in allograft and isograft to explore the relationship between this pathway and BO in rats.
We performed an orthotopic left pulmonary transplant model using the tri-cuff vascular anastomosis method and evaluated the histopathology, including the severity of fibrosis (SF). The expression of HIF-1α, VEGF-A, and VEGFR-2 was accessed by immunohistochemistry.
The imageology and pathology showed that the allogenic model developed BO 90 days after the operation. The percentages of a high expression of HIF-1α, VEGF-A, and VEGFR-2 in the allogeneic group were 77.27, 63.64, and 68.18% higher than in the isogeneic group, respectively. The SF score was highest in the allograft and was positively correlated with the expression of the proteins.
This model can simulate human BO after lung transplantation. The expression of HIF-1α and its downstream proteins in post-transplantation was up-regulated, suggesting that activation of the HIF-1α-VEGF pathway might be involved in the occurrence and prognosis of BO.
如果器官暴露于缺氧环境，移植物功能可能会受到影响。我们假设肺移植后闭塞性细支气管炎（BO）与缺氧诱导因子-1α（HIF-1α）有关。本研究比较同种异体移植和同基因移植中HIF-1α及其下游蛋白的表达，以探讨该途径与大鼠BO之间的关系。
我们采用三环血管吻合方法建立了原位左肺移植模型，并评估了组织病理学，包括纤维化严重程度（SF）。通过免疫组织化学检测HIF-1α、VEGF-A和VEGFR-2的表达。
影像学和病理学显示，同种异体模型在术后90天出现BO。同种异体组中HIF-1α、VEGF-A和VEGFR-2高表达的百分比分别比同基因组高77.27%、63.64%和68.18%。SF评分在同种异体移植中最高，且与这些蛋白的表达呈正相关。
该模型可模拟人类肺移植后的BO。移植后HIF-1α及其下游蛋白的表达上调，提示HIF-1α-VEGF途径的激活可能参与了BO的发生和预后。
