诱导型一氧化氮合酶在哮喘大鼠肺组织及中性粒细胞中的表达及地塞米松对其的影响

目的：观察诱导型一氧化氮合酶（iNOS）在哮喘大鼠肺组织及血中性粒细胞（PMN）中的表达,探讨PMN参与哮喘炎症的可能作用机制。方法：采用大鼠哮喘模型,随机分成哮喘组、对照组、地塞米松干预组,分离纯化血PMN,免疫组织化学法检测iNOS蛋白的表达水平,测定支气管肺泡灌洗液（BALF）中NO浓度。结果：哮喘组PMNiNOS蛋白光密度（OD）值（0.122±0.017）的表达水平显著高于对照组OD值（0.076±0.014）（P〈0.01）,地塞米松干预组OD值（0.089±0.013）PMNiNOS蛋白的表达水平显著低于哮喘组OD值（P〈0.01）,但与对照组相比差异无统计学意义。哮喘组支气管壁iNOS蛋白OD值（0.243±0.039）的表达水平显著高于对照组（0.119±0.016）（P〈0.01）,地塞米松干预组OD值（0.164±0.016）支气管壁iNOS蛋白的表达水平显著低于哮喘组且高于对照组（P均〈0.01）。哮喘组BALFNO浓度（8.59±1.07）ng/mL显著高于对照组（3.69±1.00）ng/mL（P〈0.01）,地塞米松干预组BALFNO浓度（4.28±0.89）ng/mL显著低于哮喘组（P〈0.01）,但与对照组相比差异无统计学意义。PMNiNOS蛋白的表达水平与BALFNO浓度呈显著正相关（n=29,r=0.770,P〈0.01）。支气管壁iNOS蛋白的表达水平与BALFNO浓度呈显著正相关（n=29,r=0.802,P〈0.01）。结论：哮喘大鼠PMN合成iNOS蛋白的功能增加,PMN可能通过iNOS参与哮喘的发病机制,这种功能可以部分被地塞米松所抑制。

Inducible nitric oxide synthase expression in lung tissue and neutrophil of asthmatic rats and the effects of dexamethasone on them

AIM:To observe the expression of inducible nitric oxide synthase (iNOS) in neutrophils and lung tissues and explore the roles of peripheral blood neutrophils in the pathogenesis of asthmatic inflammation in asthmatic rats. METHODS:Experimental rats were randomly divided into asthma, control and dexamethasone treated groups. Peripheral blood neutrophils were isolated and the expression of iNOS was detected by immunohistochemistry. The nitric oxide (NO) concentration of bronchoalveolar lavage fluids (BALF) was also determined. RESULTS:iNOS protein of PMN in asthmatic rats (0. 122 + 0.017 Optical density) was significantly higher than that in control group (0. 076±0.014, P ＜0.01). iNOS protein of PMN in dexamethasone treated group (0.089±0.013) was markedly lower than that in asthma group ( P ＜ 0.01 ), but there was no statistically significant for the PMN iNOS expression between the dexamethasone treated group and control group. Furthermore, iNOS of bronchial wall in asthma group (0.243±0.039) was dramatically higher than that in control group (0. 119 + 0.016,P ＜ 0.01 ). iNOS in dexamethasone treated group (0. 164±0.016) was significantly lower than that in asthma group, but was higher than that in control group (P ＜0.01, respectively). NO concentration of BALF in asthma group (8.59±1.07) ng/mL was significantly higher than control group (3.69 + 1.00 ng/mL, P＜ 0.01 ). NO concentration of BALF in dexamethasone treated group (4.28±0.89) ng/mL was significantly lower than that in asthma group, while no significance was observed between the indexamethasone treated and control group. Moreover, iNOS protein expression of PMN was highly correlated with NO concentration of BALF (n=29, r = 0. 770, P ＜ 0.01 ), and a similar strong association was established between the bronchial wall iNOS and NO concentration of BALF (n = 29, r= 0. 802, P ＜ 0.01 ). CONCLUSION: iNOS of PMN was elevated in asthmatic rats, which could be partly inhibited by dexamethasone. Our study indicated that an increased iNOS expression of PMN may involved in the pathogenesis of asthma in rats.