摘要
目的探讨一氧化氮（ＮＯ）及其合酶（ＮＯＳ）在哮喘发病机制中的作用。方法采用哮喘豚鼠模型，将豚鼠分为４组：（１）哮喘组（１３只），用１０％卵白蛋白腹腔注射１ｍｌ致敏，２周后用１％卵白蛋白超声雾化吸入致其哮喘发作。（２）肾上腺皮质激素预防组（激素组１３只）；诱喘同哮喘组，在每次诱喘前腹腔滴注地塞米松０５ｍｇ／ｋｇ。（３）硝基精氨酸甲酯预防组（ＬＮＮＡ组１３只）：诱喘同哮喘组，每次诱喘前腹腔注射ＬＮＮＡ０４ｍｇ／ｋｇ。（４）正常对照组（１３只）：用生理盐水代替诱喘剂。每组分别测定其血浆、支气管肺泡灌洗液（ＢＡＬＦ）和肺组织ＮＯ２／ＮＯ３水平，肺组织诱导型（ｉＮＯＳ）和原生型（ｃＮＯＳ）一氧化氮合酶活性水平，并用组织化学染色法观察了ＮＯＳ在豚鼠哮喘模型肺组织中的分布。结果４组豚鼠血浆ＮＯ２／ＮＯ３水平差异无显著性（Ｐ均＞０．０５）。哮喘组ＢＡＬＦ及肺组织中ＮＯ２／ＮＯ３和肺组织ｉＮＯＳ活性水平均明显高于其它３组（哮喘组ＢＡＬＦ中ＮＯ２／ＮＯ３，ｔ分别＝７．３７、４９５、４４８，Ｐ均＜０．０１；哮喘组肺组织中ＮＯ２／ＮＯ３，ｔ分别＝２３．３４、１８１０、１６１２，Ｐ均＜０．０１；哮喘?
Objective To investigate the role of nitric oxide (NO) and nitric oxide synthase (NOS) in the pathogenesis of asthma. Method 52 guinea pigs were randomly divided into four groups of 13 each: (1) asthmatic group (Group A): Dunkin Hartley guinea pigs were injected celiacly with 1 ml of 10% ovalbumin (OA). After 14 days, the animals were inhaled with an aerosol of 1% OA for 40～60 seconds for 10 days every other day; (2) Corticosteroid prevention group (Group CT): As above, just before the animals were inhaled with an aerosol, 0.5 mg/kg dexamethasone were injected celiacly ; (3) N nitro L arginine prevention group (Group L): As Group A, just before the animals were inhaled with an aerosol, 0.4 mg/kg LNNA were injected celiacly; (4) Controls (Group C): and nitrate (NO 2/NO 3) levels in plasma, nitrite bronchoalveolar lavage fluid (BALF) and lung tissues were examined . At the same time, inducible nitric oxide synthase (iNOS) and constitute nitric oxide synthase (cNOS) activity levels in the lung tissues were examined, and the changes of cNOS in the guinea pig asthma model lung tissues were observed using histochemical detection. Result All groups had no significant alteration of NO 2/NO 3 in the plasma ( P >0.05). Group A had increased amounts of NO 2/NO 3 in the BALF and in the lung tissues compared with the other groups (BALF: Group A 10.2±1.3, Group CT 7.2±1.1, Group L 7.3±1.3, Group C 6.2±0.8 μmol/L respectively, all of P <0.01; the lung tissues: Group A 0.89±0.07, Group CT 0.16± 0.09, Group L 0.24±0.09, Group C 0.18±0.05 nmol/mg respectively, all of P <0.01). Group A also showed increased amounts of iNOS levels in the lung tissues than the other groups (Group A 59±18, Group CT 10±5, Group L 12±7, Group C 10±5 pmol/mg respectively, all of P <0.01). Group L showed decreased amounts of cNOS levels in the lung tissues than the Group C (0.8±0.4, 1.2±0.4 fmol/mg, P < 0.05). While there were no significant alterations in the other groups ( P > 0.05). Elevation of iNOS in the lung tissues was correlated with NO 2/NO 3 in the BALF and in the lung tissues ( r =0.714, 0.842, respectively, P <0.05, 0.01 respectively). NADPHd was found to be a histochemical marker reflecting cNOS activity. It was found that there was no marked alteration of cNOS activity in the Group A, Group CT and Group C, but lower in the Group L. Conclusion There is increased production of iNOS in asthmatic guinea pigs, the iNOS produced could cause increased production of NO, and probably cause cytotoxicity and mediate airway hyperresponsiveness. NO and NOS may play an important role in the pathogenesis of asthma.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
1998年第4期204-207,共4页
Chinese Journal of Tuberculosis and Respiratory Diseases
