Nitric oxide in liver diseases - Friend, foe, or just passerby?
Nitric oxide in liver diseases - Friend, foe, or just passerby?
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DOI：
10.1111/j.1749-6632.2002.tb04074.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Khoo, HE
中科院分区：
文献类型：
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作者：
Hon, WM;Lee, KH;Khoo, HE
近二十年来，对自由基气体一氧化氮（NO）的研究是生物学中发展最为迅速的领域之一。NO似乎在几乎每个器官和组织中都起作用。然而，在理解其作用方面存在相当大的争议和混乱。肝脏是一个明显受NO影响的器官。急性或慢性暴露于NO与不同类型的肝脏疾病有关。在本文中，我们回顾和讨论一氧化氮在各种肝脏疾病的参与从不同的研究人员的观察整理。总的来说，决定一氧化氮有益与有害影响的重要因素是一氧化氮产生的数量、持续时间和位置。在急性脓毒症和再灌注事件中，低剂量NO可以最大化血液灌注，防止血小板聚集和血栓形成，中和肝脏中的有毒氧自由基。一氧化氮在急性肝炎感染和其他炎症过程中也显示出抗菌和抗细胞凋亡的特性。然而，在慢性肝脏炎症的情况下，当NO持续大量存在时，NO可能具有遗传毒性并导致肝癌的发展。此外，在长时间缺血期间，高水平的NO可能具有细胞毒性作用，导致严重的肝损伤。鉴于NO可能发挥的多种作用，在未来肝脏疾病的治疗中，特别是随着选择性NO合成酶抑制剂和细胞特异性NO供体的出现，对NO合成的药理学调节是有希望的。
Research on the free radical gas, nitric oxide (NO), during the past twenty years is one of the most rapid growing areas in biology. NO seems to play a part in almost every organ and tissue. However, there is considerable controversy and confusion in understanding its role. The liver is one organ that is clearly influenced by NO. Acute versus chronic exposure to NO has been associated with distinct patterns of liver disease. In this paper we review and discuss the involvement of NO in various liver diseases collated from observations by various researchers. Overall, the important factors in determining the beneficial versus harmful effects of NO are the amount, duration, and site of NO production. A low dose of NO serves to maximize blood perfusion, prevent platelet aggregation and thrombosis, and neutralize toxic oxygen radicals in the liver during acute sepsis and reperfusion events. NO also demonstrates antimicrobial and antiapoptosis properties during acute hepatitis infection and other inflammatory processes. However, in the setting of chronic liver inflammation, when a large sustained amount of NO is present, NO might become genotoxic and lead to the development of liver cancer. Additionally, during prolonged ischemia, high levels of NO may have cytotoxic effects leading to severe liver injury. In view of the various possible roles that NO plays, the pharmacologic modulation of NO synthesis is promising in the future treatment of liver diseases, especially with the emergence of selective NO synthase inhibitors and cell-specific NO donors.