Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects
Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects
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DOI：
10.1016/s0002-9440(10)63646-2
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发表时间：
2003-07-01
影响因子：
6
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Song, RP;Kubo, M;Choi, AMK
肺移植的成功一直受到急性排斥反应发生率高的限制。越来越多的证据表明，应激反应基因血红素加氧酶-1（HO-1）和/或其催化副产物一氧化碳（CO）赋予细胞保护作用，以对抗组织和细胞损伤。这使我们假设CO可能通过其抗炎和抗凋亡作用来保护肺移植排斥反应。在来自Brown-Norway大鼠供体的刘易斯大鼠受体中进行原位左肺移植。与假手术对照组相比，移植肺HO-1 mRNA和蛋白表达明显增加。移植的肺出现严重的肺泡内出血、明显的炎性细胞浸润和血管内凝血。然而，在存在CO暴露（500 ppm）的情况下，移植肺的大体解剖和组织学显示出明显的保存。此外，与CO暴露受体的移植肺相比，移植肺显示出增加的凋亡细胞死亡，如通过TUNEL和caspase-3免疫染色所评估的。CO暴露可抑制肺组织和血清中IL-6 mRNA和蛋白表达的诱导。基因阵列分析显示，CO还下调了其他促炎基因，包括MEP-1 α和MIF，以及生长因子，如血小板衍生生长因子，这些基因在移植中上调。这些数据表明，在大鼠肺移植模型中，CO的抗炎和抗凋亡特性赋予有效的细胞保护作用。
Successful lung transplantation has been limited by the high incidence of acute graft rejection. There is mounting evidence that the stress response gene heme oxygenase-1 (HO-1) and/or its catalytic by-product carbon monoxide (CO) confers cytoprotection against tissue and cellular injury. This led us to hypothesize that CO may protect against lung transplant rejection via its anti-inflammatory and antiapoptotic effects. Orthotopic left lung transplantation was performed in Lewis rat recipients from Brown-Norway rat donors. HO-1 mRNA and protein expression were markedly induced in transplanted rat lungs compared to sham-operated control lungs. Transplanted lungs developed severe intraalveolar hemorrhage, marked infiltration of inflammatory cells, and intravascular coagulation. However, in the presence of CO exposure (500 ppm), the gross anatomy and histology of transplanted lungs showed marked preservation. Furthermore, transplanted lungs displayed increased apoptotic cell death compared with the transplanted lungs of CO-exposed recipients, as assessed by TUNEL and caspase-3 immunostaining. CO exposure inhibited the induction of IL-6 mRNA and protein expression in lung and serum, respectively. Gene array analysis revealed that CO also down-regulated other proinflammatory genes, including MEP-1alpha and MIF, and growth factors such as platelet-derived growth factor, which were up-regulated by transplantation. These data suggest that the anti-inflammatory and antiapoptotic properties of CO confer potent cytoprotection in a rat model of lung transplantation.