Nakao Atsunori, Kimizuka Kei, Stolz Donna B, Seda Neto Joao, Kaizu Takashi, Choi Augustine M K, Uchiyama Takashi, Zuckerbraun Brian S, Bauer Anthony J, Nalesnik Michael A, Otterbein Leo E, Geller David A, Murase Noriko
University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Surgery. 2003 Aug;134(2):285-92. doi: 10.1067/msy.2003.238.
Heme oxygenase (HO)-1 system has been shown to provide protection against oxidative stress through the degradation of heme to biliverdin, free iron, and carbon monoxide (CO). This study investigated cytoprotective efficacy of CO at a low concentration on cold ischemia/reperfusion (I/R) injury of transplanted intestine.
Lewis rat recipients of syngenic orthotopic small intestinal transplantation with 6 hours UW cold preservation were either kept in room air (air-treated control) or exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery.
In air-treated grafts, mRNA levels for interleukin-6, intracellular adhesion molecule-1, cyclooxygenase-2, and inducible nitric oxide synthase promptly increased. Sequential histopathologic analysis of untreated grafts revealed initial rapid epithelial loss, subsequent recruitment of inflammatory infiltrates, and local hemorrhage in the lamina propria, which extended downward to the epithelial crypt and muscle layer with time. CO effectively blocked proinflammatory cascade during I/R injury, inhibited upregulation of inflammatory molecules and ameliorated intestinal tissue injuries. Beneficial effects of CO were associated with improved graft blood flow without inhibiting endogenous HO-1 activity. Recipient animal survival was significantly improved with CO to 100% versus 58% in air-treated controls.
These results indicate a significant role for CO in protecting the intestine from cold I/R injury associating with small intestinal transplantation.
血红素加氧酶（HO）-1系统已被证明可通过将血红素降解为胆绿素、游离铁和一氧化碳（CO）来抵御氧化应激。本研究调查了低浓度CO对移植肠冷缺血/再灌注（I/R）损伤的细胞保护作用。
将接受6小时UW冷保存的同基因原位小肠移植的Lewis大鼠受体，术后分别置于室内空气环境（空气处理对照组）或暴露于CO（250 ppm）中1小时，术前和术后各24小时。
在空气处理的移植物中，白细胞介素-6、细胞间黏附分子-1、环氧化酶-2和诱导型一氧化氮合酶的mRNA水平迅速升高。未经处理的移植物的连续组织病理学分析显示，最初上皮迅速丢失，随后炎症浸润细胞募集，固有层局部出血，并随时间向下延伸至上皮隐窝和肌层。CO有效阻断了I/R损伤期间的促炎级联反应，抑制了炎症分子的上调，减轻了肠道组织损伤。CO的有益作用与改善移植物血流有关，且未抑制内源性HO-1活性。与空气处理对照组58%的存活率相比，CO使受体动物存活率显著提高至100%。
这些结果表明CO在保护小肠免受与小肠移植相关的冷I/R损伤中起重要作用。
