Barshes Neal R, Wyllie Samuel, Goss John A
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Suite 1628, Houston, TX 77030, USA.
J Leukoc Biol. 2005 May;77(5):587-97. doi: 10.1189/jlb.1104649. Epub 2005 Feb 22.
Recent advances in clinical protocols have improved the outcomes of pancreatic islet transplantation (PIT), yet PIT recipients typically require pancreatic islet grafts derived from multiple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involvement of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1beta appears to be among the most important inflammatory mediators, causing pancreatic islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer cells improves outcomes following experimental PIT. Immediately after transplantation, the pancreatic islets are perfused only by portal vein blood until the process of angiogenesis restores arterial blood flow some 7-10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion molecules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the immediate post-transplant period, hepatocytes may contribute to pancreatic islet injury through the production of NO. This paper reviews literature regarding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic ischemia-reperfusion and their relation to the survival and function of intrahepatic pancreatic islet grafts.
临床方案的最新进展改善了胰岛移植（PIT）的效果，但PIT受者通常需要来自多个供体的胰岛移植才能实现胰岛素自主分泌。这一点，再加上同基因PIT的实验模型表明，高达60%的胰岛组织在移植后的头几天内会发生凋亡，强烈提示非同种抗原特异性的炎症事件参与了PIT后移植物的部分破坏。白细胞介素-1β似乎是最重要的炎症介质之一，它通过上调诱导型一氧化氮合酶和环氧化酶-2导致胰岛功能障碍和凋亡。库普弗细胞分泌许多分子，包括细胞因子、一氧化氮和自由基，已知这些分子对胰岛具有直接毒性，去除或抑制库普弗细胞可改善实验性PIT后的结果。移植后立即，胰岛仅由门静脉血灌注，直到血管生成过程在约7-10天后恢复动脉血流。这种延迟的血管化可能对白细胞粘附分子的表达、自由基的作用以及缺血再灌注损伤的作用产生影响。最后，在移植后的即刻，肝细胞可能通过产生一氧化氮导致胰岛损伤。本文综述了有关PIT后炎症事件以及糖尿病发病机制、肝脏缺血再灌注病理生理学及其与肝内胰岛移植存活和功能关系的文献。
