Weiss S, Kotsch K, Francuski M, Reutzel-Selke A, Mantouvalou L, Klemz R, Kuecuek O, Jonas S, Wesslau C, Ulrich F, Pascher A, Volk H-D, Tullius S G, Neuhaus P, Pratschke J
Department of Surgery, Charité, Campus Virchow Clinic, Universitätsmedizin Berlin, Germany.
Am J Transplant. 2007 Jun;7(6):1584-93. doi: 10.1111/j.1600-6143.2007.01799.x. Epub 2007 Apr 8.
The majority of transplants are derived from donors who suffered from brain injury. There is evidence that brain death causes inflammatory changes in the donor. To define the impact of brain death, we evaluated the gene expression of cytokines in human brain dead and ideal living donors and compared these data to organ function following transplantation. Hepatic tissues from brain dead (n = 32) and living donors (n = 26) were collected at the time of donor laparotomy. Additional biopsies were performed before organ preservation, at the time of transplantation and one hour after reperfusion. Cytokines were assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and cytometric bead array. Additionally, immunohistological analysis of tissue specimens was performed. Inflammatory cytokines including IL-6, IL-10, TNF-alpha, TGF-beta and MIP-1alpha were significantly higher in brain dead donors immediately after laparotomy compared to living donors. Cellular infiltrates significantly increased in parallel to the soluble cytokines IL-6 and IL-10. Enhanced immune activation in brain dead donors was reflected by a deteriorated I/R injury proven by elevated alanin-amino-transferase (ALT), aspartat-amino-transferase (AST) and bilirubin levels, increased rates of acute rejection and primary nonfunction. Based on our clinical data, we demonstrate that brain death and the events that precede it are associated with a significant upregulation of inflammatory cytokines and lead to a worse ischemia/reperfusion injury after transplantation.
大多数移植器官来源于脑损伤的供体。有证据表明脑死亡会导致供体发生炎症变化。为了确定脑死亡的影响，我们评估了脑死亡供体和理想活体供体中细胞因子的基因表达，并将这些数据与移植后的器官功能进行了比较。在供体剖腹手术时收集脑死亡供体（n = 32）和活体供体（n = 26）的肝组织。在器官保存前、移植时和再灌注后1小时进行额外的活检。通过实时逆转录聚合酶链反应（RT-PCR）和细胞计数珠阵列评估细胞因子。此外，还对组织标本进行了免疫组织学分析。与活体供体相比，剖腹手术后立即脑死亡供体中的炎症细胞因子，包括白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）和巨噬细胞炎性蛋白-1α（MIP-1α）显著更高。细胞浸润与可溶性细胞因子IL-6和IL-10平行显著增加。脑死亡供体中增强的免疫激活表现为丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和胆红素水平升高、急性排斥反应和原发性无功能发生率增加所证实的缺血/再灌注损伤恶化。基于我们的临床数据，我们证明脑死亡及其之前的事件与炎症细胞因子的显著上调相关，并导致移植后更严重的缺血/再灌注损伤。
