Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Gut. 2013 Apr;62(4):616-29. doi: 10.1136/gutjnl-2011-301649. Epub 2012 Jan 20.
Throughout the human gastrointestinal tract a variety of reactive nitrogen oxides are continuously formed as a result of a complex interplay between the host, commensal bacteria and dietary factors. These compounds include nitric oxide, nitrite, nitrate, peroxynitrite, S-nitrosothiols, nitrated fatty acids and N-nitrosamines, all of which are bioactive with the potential to affect physiological and pathological processes locally in the gut as well as systemically after absorption. Historically, the literature has been dominated by studies on the formation of potentially carcinogenic nitrosamines, but the focus was shifted in the 1980s with the seminal discovery of the L-arginine-nitric oxide pathway and its profound impact on normal physiological functions. More recently, a nitrate-nitrite-nitric oxide pathway has been discovered, with implications for local host defence and gut mucosal integrity and, intriguingly, also for systemic regulation of cardiovascular and metabolic function. This review discusses recent advances in the understanding of the formation, biochemistry, physiology and pathophysiology of reactive nitrogen oxides in the gastrointestinal tract. In addition, opportunities for nitric oxide-based pharmacological or dietary interventions are highlighted.
在整个人体胃肠道中，由于宿主、共生细菌和饮食因素之间的复杂相互作用，各种反应性氮氧化物不断形成。这些化合物包括一氧化氮、亚硝酸盐、硝酸盐、过氧亚硝酸盐、S-亚硝基硫醇、硝化脂肪酸和 N-亚硝胺，它们都具有生物活性，有可能在肠道局部以及吸收后全身影响生理和病理过程。从历史上看，文献主要集中在可能致癌的亚硝胺的形成研究上，但随着 L-精氨酸-一氧化氮途径的开创性发现及其对正常生理功能的深远影响，研究重点在 20 世纪 80 年代发生了转移。最近，发现了一种硝酸盐-亚硝酸盐-一氧化氮途径，这对局部宿主防御和肠道黏膜完整性具有重要意义，而且令人感兴趣的是，它也与心血管和代谢功能的全身调节有关。本文综述了近年来对胃肠道中反应性氮氧化物的形成、生物化学、生理学和病理生理学的理解进展。此外，还强调了基于一氧化氮的药理学或饮食干预的机会。
