Kubes P, McCafferty D M
Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Am J Med. 2000 Aug 1;109(2):150-8. doi: 10.1016/s0002-9343(00)00480-0.
Inflammation of the intestinal tract remains a very serious concern in the clinical setting. Unfortunately, to date, the mechanisms underlying many inflammatory conditions such as sepsis or inflammatory bowel diseases are poorly understood and our therapeutic interventions are less than ideal. Over the past decade, an abundance of research has been directed toward the role of nitric oxide (NO) in intestinal inflammation. It has become apparent that NO might have a dichotomous role as both a beneficial and detrimental molecule. Nitric oxide is a weak radical produced from L-arginine via the enzyme nitric oxide synthase (NOS). NOS exists in three distinct isoforms; constitutively (cNOS) expressed neuronal NOS (NOS1 or nNOS) and endothelial NOS (NOS3 or eNOS) or an inducible isoform (NOS2 or iNOS) capable of high production output of NO during inflammation. Constitutively expressed NOS has been shown to be critical to normal physiology and inhibition of these enzymes (nNOS or eNOS) caused damage. It has been proposed that the high output production of NO from iNOS causes injury, perhaps through the generation of potent radicals such as peroxynitrite and hence may explain the apparent dichotomous role of NO. However, recent studies have challenged this simple paradigm providing evidence that iNOS may have some protective role in some inflammatory models. Moreover, the importance of peroxynitrite has been questioned. In this review we discuss the role of cNOS and iNOS in intestinal inflammation and provide an overview of peroxynitrite in intestinal inflammation, highlighting some of the controversy that exists.
在临床环境中，肠道炎症仍然是一个非常严重的问题。不幸的是，迄今为止，许多炎症性疾病（如败血症或炎症性肠病）的潜在机制仍知之甚少，我们的治疗干预措施也不尽如人意。在过去十年中，大量研究致力于一氧化氮（NO）在肠道炎症中的作用。很明显，NO可能具有双重作用，既是有益分子又是有害分子。一氧化氮是一种由L-精氨酸通过一氧化氮合酶（NOS）产生的弱自由基。NOS存在三种不同的同工型；组成型（cNOS）表达的神经元型NOS（NOS1或nNOS）和内皮型NOS（NOS3或eNOS），或者是一种诱导型同工型（NOS2或iNOS），在炎症期间能够大量产生NO。已证明组成型表达的NOS对正常生理功能至关重要，抑制这些酶（nNOS或eNOS）会导致损伤。有人提出，iNOS产生的大量NO会造成损伤，可能是通过产生如过氧亚硝酸盐等强自由基，因此这可能解释了NO明显的双重作用。然而，最近的研究对这一简单模式提出了挑战，提供证据表明iNOS在某些炎症模型中可能具有一些保护作用。此外，过氧亚硝酸盐的重要性也受到了质疑。在这篇综述中，我们讨论了cNOS和iNOS在肠道炎症中的作用，并概述了过氧亚硝酸盐在肠道炎症中的情况，突出了存在的一些争议。
