诱导型一氧化氮合酶抑制剂的研究进展  

Advances in the study of inducible nitric oxide synthase inhibitors

作　　者：李园园[1] 徐文清[1] 

机构地区：[1]中国医学科学院北京协和医学院放射医学研究所,天津300192

出　　处：《中国药物化学杂志》2017年第6期477-489,共13页Chinese Journal of Medicinal Chemistry

基　　金：天津市应用基础与前沿技术研究重点项目(14JCZDJC36400)

摘　　要：一氧化氮(NO)是一种信号分子及自由基,参与哺乳动物体内许多重要生理过程,而且它在炎症和肿瘤疾病中发挥着重要作用。内源性的NO由一氧化氮合酶(NOSs)催化氧化L-精氨酸产生,人类一氧化氮合酶分为三种主要类型,包括神经元型(nNOS)、内皮型(eNOS)和诱导型(iNOS)。其中诱导型一氧化氮合酶(iNOS)是钙离子非依赖型的并且会被外部刺激如炎性细胞因子和氧化应激(如TNF-α、IL-1β、PS、γ-射线、氧化物)激活。由i NOS产生的过量的NO会导致多种疾病。而且证据表明,对iNOS有效的抑制在预防和治疗炎症和肿瘤疾病、免疫紊乱、组织损伤、败血性休克、糖尿病和辐射诱导的血管内皮细胞损伤等方面都是有效的。因此iNOS抑制剂作为一个新的靶点及治疗途径,具有重要的医疗价值,本文综述了当前i NOS抑制剂的研究进展。Nitric oxide（NO） is a signaling molecule and free radical, involved in many important physiological processes in mammals, and it plays crucial roles in inflammation and neoplastic diseases. Nitric oxide synthases（NOS） are a family of enzymes that play an essential role in synthesizing nitric oxide （NO） by oxidizing L-arginine, which have been classified as neuronal （ nNOS ）, endothelial （ eNOS ） and inducible （iNOS） isoforms, iNOS is calcium-independent and activated by external stimuli such as inflammatory cytokines and oxidative stress （such as tumor necrosis factor-α, interleukin-1β, lipopolysaccharide, oxidants and γ-ray irradiation, etc. ）. The excess production of NO derived from iNOS has been implicated in numerous diseases. There are also mounting pieces of evidences that the inhibition of iNOS may be beneficial in prevention and treatment of inflammatory and tumor diseases, immune dysfunction, tissue damage, septic shock, diabetes and radiation-induced vascular endothelial damage, etc. Therefore, inducible nitric oxide syn- thase inhibitors as a novel target and therapeutic approach, has significant medical value. This review summarizes relevant researches of iNOS inhibitors to date.

关 键 词：一氧化氮 诱导型一氧化氮合酶 INOS抑制剂 

分 类 号：R91[医药卫生—药学]