氯胺酮雾化吸入对哮喘大鼠肺一氧化氮合酶表达的影响
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江苏省自然科学基金资助项目(BK2001160)


Effect of nebulized ketamine on expression of nitric oxide synthase in the lungs of asthm-atic rats
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    摘要:

    目的:探讨氯胺酮雾化吸入对哮喘大鼠肺一氧化氮合酶(NOS)表达的影响。方法: 40只Brown Norway大鼠随机分为对照组(C组)、哮喘模型组(A组)、氯胺酮1组(K1组)、氯胺酮2组(K2组)、氯胺酮3组(K3组),每组8只。A组用卵蛋白辅以百日咳杆菌菌苗及氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发。K1、K2、K3组大鼠以同样方法致敏,在激发前分别雾化吸入12.5、25.0、50.0 mg/ml的氯胺酮。C组注射和雾化吸入PBS。取肺组织提取RNA,以RT-PCR法分析NOS mRNA的表达,并作肺组织病理学检查。结果:A组肺组织切片显示为急性气道炎症性改变,与A组相比,K1、K2、K3组炎症状态明显减轻。iNOS mRNA的表达与C组比较,A组明显增强,并有显著性差异(P < 0.01),与A组比较,K1、K2、K3组iNOS mRNA表达明显减弱,有显著性差异(K1组P < 0.05,K2组、K3组P < 0.01)。K1、K2、K3组间无明显差异。eNOS mRNA各组表达无显著性差异,nNOS在各组呈微弱表达。结论:氯胺酮雾化吸入可抑制卵蛋白所致的大鼠肺iNOS mRNA高表达,并改善肺部炎症,对肺损伤有保护作用。雾化吸入氯胺酮12.5 mg/ml已达到治疗效果。

    Abstract:

    Objective:To investigate the effect of nebulized ketamine inhalation on the expression of nitric oxide synthase(NOS) in the lungs of asthmatic rats. Methods:Forty Brown Norway rats(10-12 weeks) were randomly assigned to five groups, with eight animals each, which were control group(C), asthma group(A), and ketamine pretreated groups(K1,K2,K3). In group A,K1,K2,K3, asthma was induced in two steps:receiving subcutaneous injection of ovalbumia(OVA)1 mg and aluminum hydroxide 160 mg in 1ml of PBS, and then inhaling nebulized 1% OVA in PBS for 30 min. In group K1, K2 and K3, the sensitized rats were exposed to 12.5 mg/ml(K1 group),25 mg/ml(K2 group),50 mg/ml(K3 group) of nebulized ketamine for 30 min. Lung samples were taken and total RNA were isolated, NOS mRNA were determined with RT-PCR. The right lung was removed for microscopic examination. Results:There were acute airway inflammation changes in group A. Compared with group A, there was significantly less inflammation in the bronchial subnucosa and alveolar septum in group K1,K2 and K3. Compared with group C, the expression of iNOS mRNA was significantly higher in group A(P < 0.01). Compared with group A, the expression of iNOS was significantly less in group K1(P < 0.05), K2 (P < 0.01) and K3(P < 0.01). There was no significant difference between group K1,K2 and K3 in expression of eNOS mRNA. The expression of nNOS was low in all groups. Conclusion:Inhalation of nebulized ketamine can restrain the expression of iNOS mRNA in lung in asthmatic rats and has a protective effect on airway against inflammation and tissue damage. 12.5 mg/ml nebulized ketamine appears to be enough for satisfactory clinical results.

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戎海波,傅诚章,朱敏敏,徐玉民.氯胺酮雾化吸入对哮喘大鼠肺一氧化氮合酶表达的影响[J].南京医科大学学报(自然科学版),2007,(1):47-50

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  • 收稿日期:2006-07-09
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