一氧化氮在哮喘发病机制中的作用

目的通过观察一氧化氮合成酶（ＮＯＳ）抑制剂亚硝基左旋精胺酸甲酯（Ｌ－ＮＡＭＥ）对豚鼠离体气管张力收缩的影响及采用组织化学方法观察ＮＯＳ在豚鼠哮喘模型肺中的分布，了解一氧化氮（ＮＯ）在哮喘发病机制中的作用。方法用Ｌ－ＮＡＭＥ孵育豚鼠离体气管段后，观察对组织胺量效曲线的影响并与对照组比较；另用还原型辅酶ＮＡＤＰＨ－ｄ对豚鼠哮喘模型肺组织行组织化学染色。结果豚鼠离体气管段经Ｌ－ＮＡＭＥ孵育后，组胺诱发的张力曲线明显左移，其最大反应张力是对照组的１７０％（Ｐ＜０．０１）。ＮＡＤＰＨ组化染色可见哮喘模型组肺泡巨噬细胞显著增多，ＮＯＳ染色呈明显阳性反应，对照组肺泡巨噬细胞数极少，且未见ＮＯＳ染色阳性者。结论Ｌ－ＮＡＭＥ使组胺对豚鼠离体气管段收缩张力显著增加，通过增加ＮＯ生成可降低气道对组胺的反应性；哮喘时肺泡巨噬细胞显著增多，且ＮＯＳ染色呈明显阳性。提示在巨噬细胞中的ＮＯＳ作用下产生的ＮＯ在哮喘发病中起重要作用。

The role of nitric oxide in the pathogenesls of asthma

Objective To investigate the role of nitric oxide (NO) in the pathogenesis of asthma,we observed the influence of L N G arginine methylester(L NAME),the inhibitor of nitric oxide synthase(NOS),on the contraction of isolated guinea pig tracheal smooth muscles and observed the changes of NOS in the guinea pig asthma modellung tissues using histochemical detection.Mehtods Male Hartley guinea pig isolated tracheal ring were incubated with L NAME 2.0 mmol/L for 30 min and histamine was given to make a concentration response curve.The sections of guinea pig asthma model lung tissues were stained with NADPH diaphorase .Results The histamine concentration response curve was significantly shifted upward in the L NAME incubated group,the maximal response increased by 170% compared with that of control group.The numbers of alveolar macrophages were significantly increased and NADPH diaphorase staining was positive in asthma model group,in contrast,the alveolar macrophages were hardly seen and there was almost no positive staining of NOS in the control group .Conclusions The inhibition of NO synthesis of guinea pig respiratory tract with L NAME results in a marked increase in airway contraction in vitro after histamine provocation.This result indicate that NO has relaxant effect on tracheal smooth muscles and may decrease airway responsiveness to histamine.The increased alveolar macrophages and positive stained NOS in the lung tissues of asthma model indicate that NO,which is synthesized by the NOS in alveolar macrophages,may play an important role in asthma pathogenesis.