Zweers Noëlle, Petersen Arjen H, van der Hoeven Joost A B, de Haan Aalzen, Ploeg Rutger J, de Leij Lou F M H, Prop Jochum
Department of Pathology and Laboratory Medicine, Medical Biology Section, University Hospital Groningen, Groningen, The Netherlands.
Transplantation. 2004 Nov 15;78(9):1251-8. doi: 10.1097/01.tp.0000142679.45418.96.
Many recipients of lung transplants from brain-dead donors develop bronchiolitis obliterans, a manifestation of chronic rejection. It has been shown that brain death increases inflammatory mediators and accelerates acute rejection in kidney, liver, and heart transplants. In this study, the authors investigated the hypothesis that brain death increases inflammatory mediators in the donor lung and subsequently aggravates chronic rejection of the lungs after transplantation in rats.
Brain death was induced in F344 rats by inflation of a subdurally placed balloon catheter. After 6 hr, donor lungs were assessed for influx of leukocytes, expression of cell adhesion molecules, and cytokine mRNA expression. For assessment of the lung after transplantation, lungs from brain-dead F344 rats were transplanted into WKY rats. Lung function after transplantation was monitored by chest radiographs during an observation period of 100 days. At the end of this period, the lungs were histologically examined; also, cytokine mRNA expression was measured. Lungs from ventilated living donors and living donors served as controls.
After 6 hr of brain death, influx of polymorphonuclear cells and macrophages and expression of vascular cell adhesion molecule-1 in the donor lungs was increased. After transplantation at postoperative day 100, the lung function was significantly decreased compared with allografts from living donors. In the lung allografts from brain-dead donors, histologic symptoms of chronic rejection were obvious, including severe intimal hyperplasia but without bronchiolitis obliterans. Interleukin-2 mRNA was significantly increased in allografts from brain-dead donors compared with living donors.
This study shows that brain death induces an inflammatory response in the donor lung and subsequently aggravates chronic rejection after transplantation. This may explain the clinical difference in long-term function between lungs from cadaveric donors and living donors.
许多接受脑死亡供体肺移植的受者会发生闭塞性细支气管炎，这是慢性排斥反应的一种表现。研究表明，脑死亡会增加炎症介质，并加速肾、肝和心脏移植中的急性排斥反应。在本研究中，作者探讨了脑死亡会增加供体肺中的炎症介质，进而加重大鼠肺移植后慢性排斥反应的假说。
通过向硬膜下放置的球囊导管充气诱导F344大鼠脑死亡。6小时后，评估供体肺中白细胞的流入、细胞黏附分子的表达以及细胞因子mRNA的表达。为评估移植后的肺，将脑死亡F344大鼠的肺移植到WKY大鼠体内。在100天的观察期内，通过胸部X光片监测移植后的肺功能。在此期间结束时，对肺进行组织学检查；同时，测量细胞因子mRNA的表达。通气活体供体和活体供体的肺作为对照。
脑死亡6小时后，供体肺中多形核细胞和巨噬细胞的流入以及血管细胞黏附分子-1的表达增加。术后第100天移植后，与活体供体的同种异体移植物相比，肺功能显著下降。在脑死亡供体的肺同种异体移植物中，慢性排斥反应的组织学症状明显，包括严重的内膜增生，但无闭塞性细支气管炎。与活体供体相比，脑死亡供体的同种异体移植物中白细胞介素-2 mRNA显著增加。
本研究表明，脑死亡在供体肺中诱导炎症反应，进而加重移植后的慢性排斥反应。这可能解释了尸体供体肺和活体供体肺长期功能的临床差异。
