Du J, Cui D, Tian D
Division of Respiratory Medicine, 304 Hospital, P. L. A., Beijing.
Zhonghua Jie He He Hu Xi Za Zhi. 1997 Jun;20(3):153-6.
To investigate the role of nitric oxide (NO) in the pathogenesis of asthma, we observed the influence of L-NG-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 model lung tissues using histochemical detection.
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.
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.
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.
为研究一氧化氮(NO)在哮喘发病机制中的作用,我们观察了一氧化氮合酶(NOS)抑制剂L-NG-精氨酸甲酯(L-NAME)对豚鼠离体气管平滑肌收缩的影响,并采用组织化学检测方法观察了豚鼠哮喘模型肺组织中NOS的变化。
将雄性Hartley豚鼠的离体气管环与2.0 mmol/L的L-NAME孵育30分钟,然后给予组胺以绘制浓度-反应曲线。对豚鼠哮喘模型肺组织切片进行NADPH黄递酶染色。
L-NAME孵育组的组胺浓度-反应曲线明显上移,最大反应较对照组增加了170%。哮喘模型组肺泡巨噬细胞数量显著增加,NADPH黄递酶染色呈阳性,相比之下,对照组几乎未见肺泡巨噬细胞,NOS几乎无阳性染色。
用L-NAME抑制豚鼠呼吸道NO合成可导致组胺激发后体外气道收缩明显增强。该结果表明NO对气管平滑肌有舒张作用,并可能降低气道对组胺的反应性。哮喘模型肺组织中肺泡巨噬细胞增加及NOS染色阳性表明,由肺泡巨噬细胞中的NOS合成的NO可能在哮喘发病机制中起重要作用。