硝酸甘油对哮喘患者一氧化氮内皮素的影响及机制

目的　了解哮喘患者肺泡巨噬细胞（ＡＭ） 、支气管上皮细胞（ＢＥＣ） 源性一氧化氮（ＮＯ）、内皮素（ＥＴ）的分泌状态及硝酸甘油（ＮＴＧ）对哮喘患者ＡＭ、ＢＥＣ产生ＮＯ、ＥＴ的影响及机制。方法　分离纯化了１５ 例轻、中度哮喘发作期患者、７ 名健康受试者ＡＭ、ＢＥＣ，并分为哮喘未干预组、哮喘ＮＴＧ干预组和健康对照组，用放射免疫法和镀铜镉还原法分别测定ＡＭ、ＢＥＣ培养４８ 小时上清液中ＥＴ、ＮＯ·２／ＮＯ·３ 浓度，用原位杂交的方法检测ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ、ＥＴｍＲＮＡ 的表达。结果　（１） 健康受试者ＡＭ、ＢＥＣ分泌少量ＮＯ和ＥＴ及少量ｉＮＯＳｍＲＮＡ 、ＥＴｍＲＮＡ表达；（２）哮喘患者ＡＭ、ＢＥＣ源性ＮＯ、ＥＴ水平及ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ、ＥＴｍＲＮＡ表达与各组比较差异有显著性（ Ｐ均＜ ０－０５）；（３）ＮＴＧ 促进哮喘患者ＡＭ、ＢＥＣ源性ＮＯ产生（ Ｐ均＜０－０５），明显抑制ＥＴ产生和ＥＴｍＲＮＡ 的表达，与对照组比较差异均无显著性（ Ｐ均＞ ０－０５） ，ＮＴＧ同时抑制哮喘患者ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ的表达，与健康对照组、哮喘未干预组比较差异有显著性（Ｐ均＜０－０５） ；（４） 除哮喘ＮＴＧ

Effects of nitroglycerin on nitric oxide and endothelin derived from bronchial epithelial cells and alveolar macrophages in asthma

OBJECTIVE: To investigate the changes of nitric oxide(NO) and endothelin(ET) derived from alveolar macrophages(AM) and bronchial epithelial cells (BEC), and the influences of nitroglycerin (NTG) on ET and NO in asthma. METHODS: BEC and AM from 15 patients with asthma exacerbation and 7 healthy control subjects were isolated and cultured for 48 hours. NO and ET levels in supernatants and expressions of iNOS-mRNA and ET-mRNA from cultured BEC and AM were examined by copper coated cadmiunm reduction, radioimmunoassay and in situ hybridization. RESULTS: The NO level and the ET level in supernatants, and expressions of iNOS-mRNA and ET-mRNA from BEC and AM of the untreated group were higher than those of other groups (P < 0.05, respectively); The NO level from BEC and AM in supernatants of NTG pretreated group were elevated significantly and the ET level and the expression of iNOS-mRNA and ET-mRNA were lower than those of asthma untreated group (P < 0.05, respectively); The NO, ET levels and expressions of iNOS-mRNA, ET-mRNA derived from AM were higher than those derived from BEC in patients with asthma (P < 0.05, respectively); expression of iNOS-mRNA from BEC and AM were negatively correlated with the NO level in supernatants of cultured BEC and AM from the group pretreated by NTG in asthma (r = -0.60, r = -0.59; P < 0.01). While the expression of iNOS-mRNA and ET-mRNA by BEC and AM from other groups were positively correlated with the NO level and the ET level in supernatants of BEC and AM in asthma (all r > or = 0.902; P < 0.01, respectively). CONCLUSIONS: BEC and AM from patients with asthma exacerbation secreted a large quantity of NO and ET because of the increased expressions of iNOS-mRNA and ET-mRNA; AM was the main source of elevated NO and ET in airways of patients with asthma exacerbation. NTG directly enhanced the production of NO and significantly inhibited the expression of ET-mRNA, and therefore decreased the production of ET.