TY-JUR T1 - 人类肺部修复潜在治疗靶标免疫体内肺灌注JF - 欧洲呼吸期刊JO - EUR RESPIR J DO - 10.1183 / 13993003.02222-2019 SP - 1902222 AU - Wong，AARON AU - Zamel，Ricardo Au - Yeung，Jonathan Au - 獾，Gary D. Au - Dos Santos，Claudia C. Au - Bai，Xiaohui Au - Wang，Yubo Au - Keshavjee，Shaf Au - Liu，Mingyao Y1 - 2020 / 01/01 UR - http：//Erj.ersjournals.com/content/early/2020/03/12/13993003.0222-2019.Abstract N2 - 简介EXVivo肺灌注（EVLP）技术已经开发出来评估边缘供体肺的功能，这些功能肺部有显着增加的供体肺利用率。EVLP还通过损伤特异性治疗等抗生素或纤维蛋白溶解剂如抗生素或纤维蛋白溶解剂探索的平台。We hypothesized that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation.Materials and Methods A retrospective transcriptomics analyses were performed with peripheral tissue biopsies from ‘donation after brain death’ lungs, with 46 pre/post-transplant pairs and 49 pre/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP.Results 22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death, and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, TLR/MYD88 signaling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models.Conclusion EVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Wong has nothing to disclose.Conflict of interest: Dr. Zamel has nothing to disclose.Conflict of interest: Dr. Yeung has nothing to disclose.Conflict of interest: Dr. Bader has nothing to disclose.Conflict of interest: Dr. Dos Santos has nothing to disclose.Conflict of interest: Dr. Bai has nothing to disclose.Conflict of interest: Dr. Wang has nothing to disclose.Conflict of interest: Dr. Keshavjee has nothing to disclose.Conflict of interest: Dr. Liu has nothing to disclose. ER -