Treatment with 3-aminobenzamide during ex vivo lung perfusion of damaged rat lungs reduces graft injury and dysfunction after transplantation

Ex vivo lung perfusion (EVLP) with pharmacological reconditioning may increase donor lung utilization for transplantation (LTx). 3-Aminobenzamide (3-AB), an inhibitor of poly (ADP-ribose) polymerase (PARP), reduces ex vivo lung injury in rat lungs damaged by warm ischemia (WI). Here we determined the effects of 3-AB reconditioning on graft outcome after LTx. Three groups of donor lungs were studied: Control (Ctrl): 1 hour WI + 3 hours cold ischemia (CI) + LTx; EVLP: 1 hour WI + 3 hours EVLP + LTx; EVLP + 3-AB: 1 hour WI + 3 hours EVLP + 3-AB (1 mg.mL−1) + LTx. Two hours after LTx, we determined lung graft compliance, edema, histology, neutrophil counts in bronchoalveolar lavage (BAL), mRNA levels of adhesion molecules within the graft, as well as concentrations of interleukin-6 and 10 (IL-6, IL-10) in BAL and plasma. 3-AB reconditioning during EVLP improved compliance and reduced lung edema, neutrophil infiltration, and the expression of adhesion molecules within the transplanted lungs....

采用药物复能处理的体外肺灌注（Ex vivo lung perfusion, EVLP）可提升肺移植（lung transplantation, LTx）供体肺的利用率。3-氨基苯甲酰胺（3-Aminobenzamide, 3-AB）作为多聚ADP核糖聚合酶（poly(ADP-ribose) polymerase, PARP）抑制剂，可减轻热缺血（warm ischemia, WI）损伤大鼠肺的体外肺损伤。本研究旨在明确3-AB复能处理对肺移植术后移植物预后的影响。本研究设置三组供体肺：对照组（Ctrl）：1小时热缺血+3小时冷缺血（cold ischemia, CI）+肺移植；EVLP组：1小时热缺血+3小时体外肺灌注+肺移植；EVLP+3-AB组：1小时热缺血+3小时体外肺灌注+3-AB（1 mg·mL⁻¹）+肺移植。于肺移植术后2小时，检测各组肺移植物顺应性、肺水肿程度、组织病理学特征、支气管肺泡灌洗液（bronchoalveolar lavage, BAL）中中性粒细胞计数、移植物内黏附分子的mRNA表达水平，以及支气管肺泡灌洗液与血浆中白细胞介素6、10（IL-6、IL-10）的浓度。EVLP期间应用3-AB复能处理可改善移植肺顺应性，减轻肺水肿与中性粒细胞浸润，并下调移植肺内黏附分子的表达……