CO as a novel signaling molecule modulating cell and organ function.

一氧化氮（NO）和一氧化碳（CO）等气态一氧化物作为细胞和器官功能的调节剂近年来引起了人们的极大兴趣。当暴露于内毒素、细胞因子或缺血再灌注时，肝脏通过诱导NO合成酶的活性产生比对照组更多的NO，这可以改变多种器官功能，如血管张力对儿茶酚胺的敏感性、线粒体膜电位、胆道运输和组织再生。另一方面，肝脏通过血红素加氧酶的反应组成性地产生一氧化碳。肝组织中产生的一氧化碳可以到达正弦血管，放松脂肪储存的Ito细胞——覆盖在正弦壁上的肝脏特异性微血管周细胞——从而作为血管张力的内源性调节剂。血红素氧化酶有两种同工型：血红素氧化酶-1和血红素氧化酶-2，前者可被多种应激源诱导，后者是肝脏生理条件下的主要酶活性。虽然目前尚不清楚诱导血红素加氧酶活性产生过多的一氧化碳是否会保护或损害肝脏微血管功能的完整性，但这种双刃分子的潜在重要性刚刚出现，就像一氧化氮一样，另一种气体分子被确立为神经血管介质，诱导血管细胞松弛。本文概述了这些气态氧化物在肝脏微血管功能调节中的病理生理作用。

Gaseous monoxides such as nitric oxide (NO) and carbon monoxide (CO) have recently attracted great interests as a regulator of cell and organ function. When exposed to endotoxin, cytokines or lschemia-reperfusion, the liver produces larger amounts of NO than those in the control via the activity of inducible NO synthase which can alter a variety of the organ function such as the sensitivity of vascular tone to catecholamine, mitochondrial membrane potential, biliary transport and tissue regeneration. On the other hand, the liver constitutively produces CO through the reaction of heme oxygenase. CO generated in the liver tissue can reach sinusoidal vessels and relax fat-storing Ito cells-the liver specific microvascular pericytes covering the sinusoidal wall-and thereby serves as an endogenous modulator of vascular tone. Two isoforms of the CO-generating enzyme have been characterized : heme oxygenase-1 which is inducible by a variety of stressors, and heme oxygenase-2 which constitutes the major enzyme activity under physiological conditions in the liver. Although it is still unknown whether excessive CO generation by the Inducible heme oxygenase activity may preserve or jeopardize the integrity of microvascular function in the liver, the potential importance of this double-edged molecule has just emerged much like nitric oxide, another gaseous molecule that was established as a neurovascular mediator inducing vascular cell relaxation. This manuscript provides an overview of the pathophysiological roles of these gaseous monoxides in regulation of microvascular function in the liver.