一氧化氮与肺动脉高压及基于一氧化氮信号通路的肺动脉高压治疗药物研究进展  

Advances in nitric oxide and pulmonary hypertension and therapeutic drugs based on nitric oxide signaling pathway

作　　者：刘赛利 艾可龙 胡长平 LIU Saili;AI Kelong;HU Changping(Department of Pharmacology,Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410078,China;Department of Pharmacy,Changzhi Medical College,Changzhi 046000,China;Hunan Province Key Laboratory of Cardiovascular Research,Changsha 410078,China)

机构地区：[1]中南大学湘雅药学院药理学系,湖南长沙410078 [2]长治医学院药学系,山西长治046000 [3]心血管研究湖南省重点实验室,湖南长沙410078

出　　处：《中国药理学与毒理学杂志》2023年第10期792-797,共6页Chinese Journal of Pharmacology and Toxicology

摘　　要：一氧化氮(NO)是一种重要的血管舒张因子,具有调节血管平滑肌舒张、抑制血管平滑肌细胞增殖及减少血小板聚集和血栓形成的功能,参与调节肺动脉高压的发生发展,改善肺动脉高压。为实现NO持续、受控释放和靶点特异性,大量研究致力于开发纳米载体系统递送NO供体,用于肺动脉高压的日常给药治疗。本文概述了体内NO来源及其舒血管作用机制,总结了目前针对NO信号通路的3种肺动脉高压靶向治疗药物(磷酸二酯酶5抑制剂、鸟苷酸环化酶激动剂和吸入性NO),介绍了代表性的NO供体(如有机硝酸盐、金属亚硝基化合物、亚硝酸盐和N-重氮鎓二酸盐)以及治疗肺动脉高压的纳米载体制剂(直接递送NO气体的纳米粒子、基于亚硝酸盐的NO递送系统和基于N-重氮鎓二酸盐的NO递送系统)的研究进展。As a critical vascular relaxation factor,nitric oxide(NO)regulates vascular smooth muscle relaxation,inhibits the proliferation of vascular smooth muscle cells,and reduces platelet aggregation and intravascular thrombosis.NO participates in the whole process of occurrence and development of pulmonary hypertension(PH)and improves PH.In order to achieve the sustained,controlled release and target specificity of NO,a large number of studies have been devoted to the development of nanocarrier systems to deliver NO donors for daily drug treatment of PH.This paper reviews the source of NO and its vasodilatory mechanism,while three kinds of PH therapeutic drugs targeting NO signaling are introduced,which are phosphodiesterase 5 inhibitor,soluble guanylate cyclase agonist and inhaled NO.The vasodilation of representative NO donors,including organic nitrates,metal nitroso compounds,nitrites and N-diazonium diacids,and the research progress in nanocarrier formulations for treating PH based on NO donor modification(including nanoparticles for direct delivery of NO gas,nitrite based NO delivery systems,and N-diazonium diacid based NO delivery systems)are also outlined.

关 键 词：肺动脉高压 一氧化氮 一氧化氮供体 纳米粒子 

分 类 号：R963[医药卫生—微生物与生化药学]