雾化吸入氯胺酮对哮喘大鼠肺组织一氧化氮及一氧化氮合酶的影响

Effect of aerosolized ketamine inhalation on nitric oxide and nitric oxide synthase in the lung tissue of rats with asthma

目的通过建立大鼠支气管哮喘模型,观察不同浓度氯胺酮对哮喘大鼠肺组织iNOS活性及NO含量的影响。方法SD大鼠随机分成对照组(N组)、哮喘模型组(A组)、不同浓度氯胺酮预处理组(分别为K1组、K2组)和地塞米松组(D组),每组8只。A组大鼠用卵白蛋白辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发哮喘;氯胺酮处理组大鼠用同样方法致敏,但在激发前分别给予雾化吸入氯胺酮25 g/L(K1组)和50 g/L(K2组);D组在激发前给予雾化吸入0.01%地塞米松;N组用生理盐水替代卵蛋白进行注射和吸入。每组分别测定其肺组织NO2-/NO3-水平、肺组织诱导型NOS(iNOS)和原生型NOS(cNOS)活性水平,并用免疫组织化学法观察iNOS在大鼠哮喘模型肺组织中的分布。结果A组肺组织中NO2-/NO3-和iNOS水平升高,iNOS和肺组织NO2-/NO3-水平呈高度正相关;K1、K2组肺组织中NO2-/NO3-和iNOS水平低于A组(P<0.05);D组肺组织中NO2-/NO3-和iNOS水平亦低于A组(P<0.05)。结论25 g/L或50 g/L的氯胺酮雾化吸入可抑制哮喘大鼠肺组织iNOS活性,降低NO含量,减轻大鼠肺部炎症。

Objective To observe the effect of aerosolized ketamine inhalation on nitric oxide and nitric oxide synthase in the lung tissue of rat asthma model. Methods Forty SD rats were evenly assigned to fivegroups at random： control group （group N）, asthma model group （group A）, two pretreatment groups of different concentration of ketamine （group K1, K2） and dexamethasone group（group D）. The rats in group A were sensitized with injection of ovalbumin （OA） together with aluminum hydroxide and Bordetella pertussis as adjuvants, followed by aerosolized OA challenge two weeks later; the rats in group K1 and K2 were sensitized with OA as group A, but exposed to aerosol of ketamine, in which the ketamine concentrations in the nebulizer were 25 g/L and 50 g/ L in 0.9 % sterile saline respectively; before OVA challenge, the rats in group D were exposed to aerosol of dexamethasone. The level of NO2^-/NO3 ^- in 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 the lung tissue in rat asthma model were observed with immunohistochemical staining. Results The level of NO2^-/NO3^- and activities of iNOS in lung tissues in group A were significantly higher than those of the other groups . Positive products in lung tissues shown by immunohistochemical method epithelial cells of bronchus. The highly and positively correlated appeared as brown deposits , which were mainly distributed in iNOS activity and level of NO2^-/NO3^- in lung tissues were Conclusions NO can induce airway hypei-reactivity that worsens asthma, 25 g/L or 50 g/L aerosolized ketamine inhalation can relieve the airway inflammation and decrease the iNOS expression in the lung tissue of rat asthma model,