一氧化氮及一氧化氮合酶在哮喘大鼠气道高反应中的作用

Effect of nitric oxide and nitroc oxide synthase on airway hyperresponsiveness of asthmatic rat

目的:探讨一氧化氮及一氧化氮合酶(nitricoxidesynthase,NOS)在哮喘大鼠气道炎症中的作用及激素对其活性的影响,以期为该病的预防、康复措施介入提供理论依据。方法:实验选用雄性豚鼠30只,按随机数字法将豚鼠分为3组:①哮喘组:用100g/L卵蛋白腹腔注射1mL致敏,2周后用10g/L卵蛋白超声雾化吸入致其哮喘发作。②激素组:诱喘同前,每次诱喘前腹腔内注射甲基强的松龙10mg/kg。③对照组:用生理盐水代替诱喘剂。每组分别测定其血浆和肺组织NO2-/NO3-水平、肺组织诱导型NOS(induciblenitricoxidesynthase,iNOS)和原生型NOS(constitutenitricoxidesynthase,cNOS)活性水平,并用组织化学染色法观察NOS在豚鼠哮喘模型肺组织中的分布。结果:3组豚鼠血浆NO2-/NO3-水平差异无显著性意义(P>0.05),哮喘组肺组织中NO2-/NO3-和iNOS活性水平犤(0.87±0.08)μmol/g,(56±14)nmol/g犦明显高于对照组和激素组犤(0.19±0.06)μmol/g,(12±6)nmol/g;(0.18±0.07)μmol/g,(12±5)nmol/g犦(P<0.01)。对照组肺组织化学方法显示的阳性产物呈蓝色沉淀,主要分布于各级支气管上皮细胞,哮喘组及激素组阳性产物变化不明显。哮喘组肺组织i-NOS活性水平和肺组织NO2-/NO3-水平呈高度正相关(r=0.782,P<0.05)。

AIM:To investigate the effect of nitric oxide(NO) and nitric oxide synthase(NOS) on the airway inflammation in asthmatic rat,and the effect of hormone on the activity,for providing theoretical evidences for the prevention and rehabilitation intervention of this disease.<METHODS:Thirty male guinea pigs were selected in this experiment and randomly divided into three groups:① Asthmatic group:Guinea pigs were given abdominal injection with 100 g/L 10% ovalbumin(OA) to make sensitization.After two weeks,the animals were ultrasonic atomizing inhaled 10 g/L OA to make them asthma.② Hormone group:The asthma sensitization was made as above mentioned.Before asthma,the animals were given intraperitoneal injection with 10 mg/kg artisone wyeth.③ Control group:The asthma agent was instead by saline.The levels of NO2- /NO3- in plasma and lung tissues,activities of inducible nitric oxide synthase(iNOS) and constitute nitric oxide synthase(cNOS) were measured in all groups;and the distribution of NOS in lung tissues in the guinea pig asthma models were observed using histochemical staining.<RESULTS:The differences of level of NO2- /NO3- of guinea pigs in three groups had no significant meaning(P >0.05).Activities of NO2- /NO3- and iNOS of lung tissues in the asthma group[(0.87± 0.08) μ mol/g,(56± 14) nmol/g] were significantly higher than those in the control and hormone groups[(0.19± 0.06) μ mol/g, (12± 6) nmol/g;(0.18 ± 0.07) μ mol/g,(12± 5) nmol/g](P< 0.01).Positive products of lung tissues shown by histochemical method presented as blue deposit,which were mainly distributed in epithelial cells of bronchus;while the positive products in the asthma and hormone groups had no significant changes.The iNOS activity and the level of NO2- /NO3- of lung tissues were highly positively correlated(r=0.782,P< 0.05).<CONCLUSION:NO can induce airway hyperreactivity that causes and(or) worsen asthma.Artisone wyeth can relieve the airway inflammation and decrease the iNOS expression of lung tissues in asthmatic rats.