Spindler Rahel S, Schnuelle Peter, Nickels Lukas, Jarczyk Jonas, Waldherr Rüdiger, Theisinger Sonja, Theisinger Bastian, Klotz Sarah, Tsagogiorgas Charalambos, Göttmann Uwe, Krämer Bernhard K, Yard Benito A, Hoeger Simone
1 5th Department of Medicine, University Medical Centre Mannheim, Heidelberg University, Germany. 2 Herz- und Nierenzentrum Weinheim, Germany. 3 Novaliq GmbH, Heidelberg, Germany. 4 Department of Anesthesiology, University Medical Centre Mannheim, Heidelberg University, Heidelberg, Germany.
Transplantation. 2015 May;99(5):935-41. doi: 10.1097/TP.0000000000000577.
This study investigated the potential use of N-octanoyl dopamine (NOD) in donor management to ameliorate the damage caused by brain death and ischemia-reperfusion injury in a rat model of kidney and heart transplantation.
Brain-dead Fisher rats were treated for 6 hours with either saline or saline plus NOD. Orthotopic kidney and heterotopic heart transplantation were performed in different Lewis recipient rats. The right donor kidneys were stored for biochemical analysis. Blood samples were taken from the donor and on several days after transplantation from the recipient. All grafts were harvested after 7 days.
There was no effect on donor heart rate and blood pressure under NOD treatment. The release of lactate dehydrogenase (LDH) during brain death was reduced in the NOD group. The right kidneys from NOD-preconditioned animals revealed diminished expression of the proinflammatory cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Nevertheless, there was no difference in renal infiltration with ED1 (CD68) or major histocompatibility complex (MHC) class II-positive cells. Recipients receiving a renal allograft from NOD-treated donors had a significantly better renal function at day 1 after transplantation. Banff-grading after 7 days showed significantly reduced scores for tubulitis and vasculitis in the grafts of these recipients. In the heart allograft recipients, lower plasma LDH levels were observed.
Donor preconditioning with NOD leads to better graft function and reduced acute rejection in untreated renal allograft recipients without displaying adverse effects on heart allografts.
本研究调查了N-辛酰多巴胺（NOD）在供体管理中的潜在用途，以减轻肾和心脏移植大鼠模型中脑死亡及缺血-再灌注损伤所造成的损害。
对脑死亡的Fisher大鼠用生理盐水或生理盐水加NOD处理6小时。在不同的Lewis受体大鼠中进行原位肾移植和异位心脏移植。取右侧供体肾进行生化分析。从供体采集血样，并在移植后数天从受体采集血样。7天后取出所有移植物。
NOD处理对供体心率和血压无影响。NOD组脑死亡期间乳酸脱氢酶（LDH）的释放减少。经NOD预处理动物的右侧肾脏显示促炎细胞黏附分子细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）的表达降低。然而，ED1（CD68）或主要组织相容性复合体（MHC）II类阳性细胞的肾浸润无差异。接受经NOD处理供体的肾移植受体在移植后第1天肾功能明显更好。7天后的Banff分级显示这些受体移植物中的肾小管炎和血管炎评分显著降低。在心脏移植受体中，观察到血浆LDH水平较低。
用NOD对供体进行预处理可使未处理的肾移植受体获得更好的移植物功能并减少急性排斥反应，且对心脏移植物无不良影响。
