García-González M A, Peña A S
Departamento de Gastroenterología, Vrije Universiteit, Amsterdam, Países Bajos.
Rev Esp Enferm Dig. 1998 Dec;90(12):870-6.
Nitric oxide (NO) is an important biological mediator with effects on homeostasis, neurotransmission and immune function. Chronic inflammation of the intestinal mucosa in patients in ulcerative colitis and Crohn's disease has been reported to be associated with enhanced production of NO and nitric oxide synthase (NOS) activity. Whereas small amounts of NO produced by endothelial constitutive calcium-dependent NOS may act to preserve intestinal mucosa integrity, large amounts of NO synthesised by inducible calcium-independent NOS may play a key role in further aggravation of the inflammation and may be associated with the development of intestinal mucosal injury and amplification of immune response in patients with inflammatory bowel disease (IBD). In this article we review NO pathways, mechanisms of action, functions, regulation, immunogenetics and the role played in IBD. A deeper knowledge of the NO physiopathology may allow new therapeutical approaches in IBD patients. In fact, the development of selective inhibitors of NOS isoforms could provide a novel therapeutic option in the management of IBD patients.
一氧化氮(NO)是一种重要的生物介质,对体内平衡、神经传递和免疫功能均有影响。据报道,溃疡性结肠炎和克罗恩病患者的肠道黏膜慢性炎症与NO生成增加及一氧化氮合酶(NOS)活性增强有关。由内皮型钙依赖性组成型NOS产生的少量NO可能有助于维持肠道黏膜完整性,而由诱导型钙非依赖性NOS合成的大量NO可能在炎症进一步加重中起关键作用,并且可能与炎症性肠病(IBD)患者肠道黏膜损伤的发展及免疫反应的放大有关。在本文中,我们综述了NO的信号通路、作用机制、功能、调节、免疫遗传学以及在IBD中所起的作用。对NO生理病理学的更深入了解可能会为IBD患者带来新的治疗方法。事实上,开发NOS亚型的选择性抑制剂可为IBD患者的治疗提供新的选择。