Emtiazjoo Amir M, Hu Hanbo, Lu Li, Brantly Mark L
Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida College of Medicine, Gainesville, FL.
Research Service (151), Malcom Randall VA Medical Center, Gainesville, FL.
Transplant Direct. 2019 May 29;5(6):e458. doi: 10.1097/TXD.0000000000000898. eCollection 2019 Jun.
Ischemia-reperfusion injury (IRI) after lung transplantation triggers a cascade of inflammatory changes that can contribute to acute allograft injury. This influences both the short- and long-term survival of the lung allograft. Alpha-1 antitrypsin (AAT) is a protease inhibitor with known anti-inflammatory and immune-regulatory properties that mitigate tissue damage. This study explores the protective effects of AAT in the setting of IRI utilizing a rat lung transplant model.
Orthotopic left single lung transplantation was performed from Lewis to Sprague-Dawley rats; recipients did not receive systemic immunosuppression. Before transplantation, the donor lungs were primed with either albumin (control) or AAT. Starting the day of transplantation, recipient rats also received either albumin (control) or AAT with subsequent doses administered over the next 7 days. On the eighth postoperative day, lung allografts were recovered and analyzed.
Degree of inflammatory infiltrate, as quantified by the allograft weight (g)/body weight (kg) ratio, was significantly reduced in the AAT-treated group compared with controls (3.5 vs 7.7, respectively, < 0.05). Treatment with AAT also significantly decreased allograft necrosis in treated animals, as measured by a semiquantitative score that ranged from 0 to 4 (1.25 vs 4, < 0.05). In addition, lymphocytes isolated from recipients treatment group showed significant proliferative inhibition via a mixed lymphocyte response assay in response to donor antigens.
AAT attenuates acute allograft injury and necrosis in a rat model of lung transplantation, suggesting that AAT may play a role in reducing IRI-induced inflammation.
肺移植后的缺血再灌注损伤（IRI）引发一系列炎症变化，可导致急性移植肺损伤。这会影响肺移植的短期和长期存活。α-1抗胰蛋白酶（AAT）是一种蛋白酶抑制剂，具有已知的抗炎和免疫调节特性，可减轻组织损伤。本研究利用大鼠肺移植模型探讨AAT在IRI情况下的保护作用。
将Lewis大鼠的左肺原位单肺移植到Sprague-Dawley大鼠；受体未接受全身免疫抑制。移植前，供体肺用白蛋白（对照）或AAT预处理。从移植当天开始，受体大鼠也接受白蛋白（对照）或AAT，并在接下来的7天内给予后续剂量。术后第8天，回收并分析移植肺。
与对照组相比，AAT治疗组的炎症浸润程度（通过移植肺重量（g）/体重（kg）比值量化）显著降低（分别为3.5和7.7，<0.05）。通过0至4的半定量评分测量，AAT治疗还显著降低了治疗动物的移植肺坏死（1.25对4，<0.05）。此外，通过混合淋巴细胞反应试验，从受体治疗组分离的淋巴细胞对供体抗原显示出显著的增殖抑制。
AAT可减轻大鼠肺移植模型中的急性移植肺损伤和坏死，提示AAT可能在减轻IRI诱导的炎症中发挥作用。
