Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury
Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury
复制标题
DOI：
10.1016/s0002-9440(10)63515-8
复制
发表时间：
2003-10-01
影响因子：
6
通讯作者：
Murase, N
中科院分区：
文献类型：
--
作者：
Nakao, A;Kimizuka, K;Murase, N
一氧化碳（CO）是血红素加氧酶催化血红素的副产物，已被证明具有抗炎作用。本研究探讨了吸入一氧化碳在小肠移植相关肠冷缺血再灌注损伤中的细胞保护作用。Lewis大鼠在威斯康星大学溶液中低温保存6小时后进行原位同种肠移植。检查了三组：正常未经治疗的对照组，对照组肠移植受者保持在室内空气中，受者在手术前1小时和手术后24小时暴露于CO （250 ppm）。在空气移植物中，肠道移植后白细胞介素-6、环氧化酶-2、细胞内粘附分子（ICAM-1）和诱导型一氧化氮合酶的mRNA水平迅速升高。组织病理学。分析显示严重的粘膜糜烂，绒毛充血和炎症浸润。CO有效地阻断了这些介质的早期上调，表现出较轻的组织病理学变化，并导致动物存活率从空气处理对照组的58%显著提高到92%。CO显著降低促凋亡Bax mRNA表达，上调抗凋亡Bcl-2 mRNA表达。co处理的移植物的这些变化与保存良好的CD31（+）血管内皮细胞、肠上皮细胞和毛细血管内皮细胞较少的凋亡/坏死以及移植物组织血液循环改善有关。在本研究中，CO的保护作用是通过可溶性冠酰基环化酶介导的，因为1H-(1,2,4)恶二唑（4,3- α）喹诺啉-1- 1（可溶性冠酰基环化酶抑制剂）完全逆转了CO的有益作用。围手术期低浓度CO吸入可延长冷保存时间，保护肠移植物免受缺血/再灌注损伤。
Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to exert anti-inflammatory effects. This study examines the cytoprotective efficacy of inhaled CO during intestinal cold ischemia/reperfusion injury associated with small intestinal transplantation. Orthotopic syngenic intestinal transplantation was performed in Lewis rats after 6 hours of cold preservation in University of Wisconsin solution. Three groups were examined: normal untreated controls, control intestinal transplant recipients kept in room air, and recipients exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. In air grafts, mRNA levels for interleukin-6, cyclooxygenase-2, intracellular adhesion molecule (ICAM-1), and inducible nitric oxide synthase rapidly increased after intestinal transplant. Histopathological. analysis revealed severe mucosal erosion, villous congestion, and inflammatory infiltrates. CO effectively blocked an early up-regulation of these mediators, showed less severe histopathological changes, and resulted in significantly improved animal survival of 92% from 58% in air-treated controls. CO also significantly reduced mRNA for proapoptotic Bax, while it up-regulated anti-apoptotic Bcl-2. These changes in CO-treated grafts correlated with well-preserved CD31(+) vascular endothelial cells, less frequent apoptosis/necrosis in intestinal epithelial and capillary endothelial cells, and improved graft tissue blood circulation. Protective effects of CO in this study were mediated via soluble guanylyl cyclase, because 1H-(1,2,4)oxadiazole (4,3-alpha) quinoxaline-1-one (soluble guanylyl cyclase inhibitor) completely reversed the beneficial effect conferred by CO. Perioperative CO inhalation at a low concentration resulted in protection against ischemia/reperfusion injury to intestinal grafts with prolonged cold preservation.