气道炎症中p38MAPK及核因子κB对一氧化氮合酶调控.docVIP

气道炎症中p38MAPK及核因子κB对一氧化氮合酶的调控 田伟千，傅诚章，朱敏敏 （南京医科大学第一附属医院麻醉科，江苏 南京 210029） [摘 要] 气道炎症性疾病是由多种细胞因子、炎性介质介导的变态反应性疾病，一氧化氮（NO）作为生物体内一个重要的信使分子和效应分子,参与许多生理和病理过程，大量的NO可引起气道炎症和肺损伤等不良反应。p38蛋白激酶(p38 MAPK)可能与气道炎症性疾病的发病机制密切相关，且能调控诱导型一氧化氮合酶（iNOS）mRNA 的表达及NO 的产生。同时，p38MAPK 还是NF-κB的重要上游调控因子。作为一种多极性基因调控蛋白, 核因子κB(NF-κB)能从基因转录水平调控iNOS的合成,因而对NO具有重要的调节作用。NO对p38MAPK和NF-κB也有一定的反馈调节作用。 [关键词] 气道炎症；p38MAPK；NF-κB；诱导型一氧化氮合酶；一氧化氮 P38 Mitogen activated Protein Kinase and Nuclear Factor-κB Modulate the inducible Nitric oxide Synthase in airway inflammation Tian Weiqian , Fu Chengzhang, Zhu Minmin . Department of Anesthesiology ,the First Affiliated Hospital of Nanjing Medical University , Nanjing 210029 CHINA [Abstract] Airway inflammatory disease is characterized by allergic airway inflammation,which is mediated by various cytokines and inflammatory mediators. As an important signaling and potent molecule, NO is involved in numerous pathophysiological processes in creature bodies. Excessive production of endogenous NO in airway inflammatory disease may contribute to many adverse responses ,such as airway inflammation and lung injury etc. P38 Mitogen activated Protein Kinase ,which is likely to correlate closely with the pathogenesis of airway inflammatory disease,could Modulate iNOS mRNA expression and NO production, and p38MAPK is also an important upstream regulating factor. As a multipolar gene modulin,NF-κB can modulate the biosynthesis of inducible nitric oxide synthase at the level of nuclear transcription,thereby it is a critical factor in regulating NO production.However, No also shows a feedback regulation effect on p38MAPK and NF-κB. [Key words] airway inflammation; P38 mitogen activated protein kinase; nuclear factor-κB; inducible nitric oxide synthase; nitric oxide 一氧化氮(NO) 是一种活跃的信号小分子,参与机体多种生理和病理过程。当它作为一种炎性介质时,主要由诱导型一氧化氮合酶(iNOS) 催化底物左旋精氨酸而生成。气道炎症中, NO 的大量生成与iNOS 的异常表达有关，目前已明确iNOS的调控主要取决于基因表达的调控。但iNOS 表达的具体调控机制尚未完全明确。近年来研究表明核因子κB(NF-κB) 是炎症性疾病的关键转录因子,调控着多种炎症基因的表达。它在一系列由细胞因子、炎症介质及