Therapeutic applications of carbon monoxide.
Therapeutic applications of carbon monoxide.
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DOI：
10.1155/2013/360815
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发表时间：
2013
影响因子：
--
通讯作者：
Lee PJ
中科院分区：
文献类型：
--
作者：
Knauert M;Vangala S;Haslip M;Lee PJ
血红素氧合酶-1（HO-1）是一种在多种应激状态下被诱导的受调节的酶。一氧化碳（CO）是血红素HO催化的产物。在许多情况下，CO似乎在功能上取代HO-1，并且已知CO具有内源性抗炎、抗凋亡和抗增殖作用。CO在缺氧-再氧合和缺血-再灌注模型中得到了充分研究，并已进入用于治疗几种临床实体的II期试验。在替代损伤模型中，实验室使用脓毒症、急性肺损伤和全身炎症挑战来评估CO拯救细胞、器官和生物体的能力。希望支持CO在动物模型中的保护作用的研究将转化为患者的治疗益处。CO的临床前研究现在正朝着更复杂的损伤模型发展，这些模型反映了多微生物脓毒症或两步损伤，如脓毒症并发急性呼吸窘迫综合征。此外，正在探索与CO的共同治疗和后治疗，其中在有机会进行治疗干预之前发生损伤。本综述的目的是讨论CO的潜在治疗意义，重点是肺损伤和脓毒症相关模型。
Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models.
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