硝酸甘油、地塞米松对哮喘肺泡巨噬细胞源性一氧化氮、内皮素的影响

Effects of nitriglycerin and dexamethason on nitric oxide and endothelin derived from alveolar macrophages in patients with mild and middle asthma

研究哮喘患者肺泡巨噬细胞 (AM)源性一氧化氮 (NO)、内皮素 (ET)的变化及硝酸甘油 (NTG)、地塞米松(DXM)对两者的影响及机制。对 15例轻、中度过敏性支气管哮喘发作期患者的AM(分为未干预组、DXM干预组、NTG干预组 ) ,7名健康自愿受试者的AM(未干预组 )培养 48h ,用镀铜镉还原法、放射免疫法和原位杂交法分别测定AM培养上清液中NO ,ET水平和iNOS mRNA ,ET mRNA的表达。结果发现 ,哮喘AMiNOS mRNA ,ET mRNA表达增强 ,分别导致NO ,ET水平升高 ;NTG以直接作用的方式促进AM源性NO的产生 ,反馈抑制iNOS mRNA表达并明显抑制ETmRNA的表达 ,降低ET的水平 ;DXM降低哮喘AM源性NO ,ET水平及iNOS mRNA ,ET mRNA的表达 ,尤以抑制iNOS mRNA表达和降低NO水平为甚 ,使NO ,ET处于低水平的异常状态。

Objective: To investigate the changes about nitric oxide(NO), endothelin(ET) derived from alveolar macrophages(AMs) and the effects of nitroglycerin(NTG) and mexamethason(DXM) on ET and NO in patients with mild and middle asthma. Methods: The AMs from 7 healthy control subjects and 15 patients with attacking asthma were purified, and divided into healthy control unpretreated(Group 1), asthmatic unpretreated(Group 2), asthmatic pretreated by DXM(Group 3), asthmatic pretreated by NTG(Group 4). All purified AMs were cultured for 48 hours. The NO level and ET level in supernatant and the expression of iNOS mRNA, ET mRNA of cultured AM from above subjects were examined by copper coated cadmiunm reduction, radioimmunoassay method and in situ hybridization respectively. Results: ① The AM of Group 1 secreted a little of NO, ET and expressed a little of iNOS mRNA and ET mRNA; ② The NO and ET level in supernatant and the expression of iNOS mRNA and ET mRNAin Group 2 were evidently higher than those in other groups(P<0.05, respectively); ③ The NO and ET level in supernatant and the expression of iNOS mRNA and ET mRNA in Group 3 were evidently decreased, but they were still higher than those in Group 1(P<0.05, respectively); ④ The NO level in Group 4 was higher than that in other groups(P<0.05, respectively); ⑤ The expression of iNOS mRNA was negatively correlated with the NO level(r=-0.59,P<0.05), and the expression of ET mRNA was positively correlated with the ET level(r=0.92,P<0.01) in Group 4. Conclusion: The AMs from patients with asthma exacerbation secrete a large quantity of NO and ET because of the increasing expression of iNOS mRNA, ET mRNA; DXM can inhibit the expression of iNOS mRNA and ET mRNA, and decrease NO and ET level, but the NO and ET level are still abnormal; NTG can improve directly the production of NO and inhibit significantly the expression of iNOS mRNA and ET mRNA as well as decrease the ET level. [