Use of carbon monoxide in minimizing ischemia/reperfusion injury in transplantation.
Use of carbon monoxide in minimizing ischemia/reperfusion injury in transplantation.
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DOI：
10.1016/j.trre.2011.01.004
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Murase N
中科院分区：
文献类型：
--
作者：
Ozaki KS;Kimura S;Murase N
虽然一氧化碳(CO)是有毒的，因为它能够干扰高浓度的氧气输送，但哺乳动物细胞内源性地产生一氧化碳主要是通过血红素加氧酶(HO)催化血红素来实现的。最近的研究结果表明，HO和CO的产生是维持器官生理功能完整性的关键机制，并支持低浓度CO在体内作为信号分子发挥作用并发挥显著的细胞保护作用的新范式的发展。因此，外源性递送的CO已被证明通过其抗炎、血管扩张和抗细胞凋亡功能在各种损伤模型中发挥强大的保护作用。器官移植相关的缺血再灌注(I/R)损伤是限制移植成功的主要有害因素之一。I/R损伤是一系列相互关联的复杂事件，涉及细胞损伤、细胞凋亡、强烈的炎症反应、微循环障碍和血栓形成。CO在减少I/R损伤方面有很大的潜力。本文将对CO的基本生理学、检测CO在I/R损伤模型中的有效性的临床前研究以及可能的保护机制进行综述。CO有望成为减轻移植I/R损伤的有价值的治疗分子。
Although carbon monoxide (CO) is known to be toxic due to its ability to interfere with oxygen delivery at high concentrations, mammalian cells endogenously generate CO primarily via the catalysis of heme by heme oxygenases (HO). Recent findings have indicated that HO and generation of CO serve as a key mechanism to maintain the integrity of the physiological function of organs, and supported the development of a new paradigm that CO, at low concentrations, functions as a signaling molecule in the body and exerts significant cytoprotection. Consequently, exogenously delivered CO has been shown to mediate potent protection in various injury models through its anti-inflammatory, vasodilating, and anti-apoptotic functions. Ischemia/reperfusion (I/R) injury associated with organ transplantation is one of the major deleterious factors limiting the success of transplantation. I/R injury is a complex cascade of interconnected events involving cell damage, apoptosis, vigorous inflammatory responses, microcirculation disturbance, and thrombogenesis. CO has a great potential in minimizing I/R injury. This review will provide an overview of the basic physiology of CO, preclinical studies examining efficacy of CO in I/R injury models, and possible protective mechanisms. CO could be developed to be a valuable therapeutic molecule in minimizing I/R injury in transplantation.
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影响因子：
20.1
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