一氧化氮对细菌性肺炎大鼠炎症介质的影响  

Effects of inhaled nitric oxide on inflammatory mediators in rats with bacterial pneumonia

作　　者：孙中厚[1] 孙波[1] 

机构地区：[1]复旦大学附属儿科医院呼吸急救研究室,上海200032

出　　处：《中华急诊医学杂志》2005年第6期463-466,共4页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金资助项目(30170989)

摘　　要：目的探讨吸入一氧化氮(NO)对肺炎克雷白杆菌肺炎大鼠肺部炎症介质的影响。方法健康大鼠随机分为肺炎组(P)和正常对照(C)组,P组气道注入肺炎克雷白杆菌(约1.3×108cfu只),然后分组(n=8～10)干预24h:吸入空气(PA)、NO(20×10-6,PNO)、低氧(FiO20.4,PLO)、低氧加NO(PLONO)、高氧(FiO21.0,PHO),高氧加NO(PHONO);C组吸入空气(CA)或NO(CNO)。测定肺组织原生型和诱生型NO合酶(cNOS和iNOS)活性,肿瘤坏死因子α(TNFα)和细胞间黏附分子1(ICAM1)蛋白水平及mRNA表达。结果PA组iNOS活性显著高于CA组(P<0.01),cNOS活性显著低于CA组(P<0.01);PNO、PLO、PLONO、PHO及PHONO组均可使被抑制的cNOS活性增强,PHO及PHONO可抑制iNOS活性增加;TNFα水平PA和PHONO组均显著高于CA组(P<0.01),PNO、PLO和PLONO组均显著低于PA组(P<0.01);ICAM1水平PA组显著高于CA组(P<0.01),PNO、PLONO和PHONO组分别低于PA、PLO和PHO组(P<0.01)。各组肺组织TNFα、ICAM1、内皮细胞型NOS和iNOSmRNA表达差异均无显著性。结论吸入NO和或氧气对肺炎大鼠肺内cNOS及iNOS活性具有不同调节作用;吸入NO可抑制肺组织ICAM1表达;吸入NO和或低浓度氧可降低TNFα表达。吸入NO可能通过调节急性炎症反应介质预防炎症性肺损伤。Objective To investigate effects of inhaled nitric oxide (NO) in combination with low (0.4) and high (1.0) fraction of oxygen on inflammatory mediators in rat lungs with bacterial pneumonia. Methods Pneumonia was induced by intratracheal instillation of live Klebsiella pneumoniae (1.3×10~8 colony-forming units/rat) in adult Sprague-Dawley rats. The animals were randomized to 6 groups (n=8～10) and exposed to: air (PA), air plus NO (PNO), low oxygen (PLO),low oxygen plus NO (PLONO), high oxygen (PHO), high oxygen plus NO (PHONO), for 24 h. Additional healthy rats served as controls with inhalation of air (CA) or NO (CNO). NO was given in 20×10^(-6). Constitutive and inducible NO synthase (cNOS, iNOS) activity, tumor necrosis factor (TNF)-α and intercellular adhesion molecule (ICAM)-1 and their mRNA in pulmonary homogenates were measured. Results iNOS was higher in PA than in CA (P<0.01), and cNOS lower in PA than in CA (P<0.01) and other P-groups (P<0.01). PHO and PHONO had lower iNOS than PA(P<0.01). PA and PHONO had higher TNF-α levels than CA (P<0.01), and PNO, PLO and PLONO had lower TNF-α than PA (P<0.01). PA had higher ICAM-1 levels than CA (P<0.01), PNO, PLONO and PHONO had lower ICAM-1 than PA, PLO and PHO (P<0.01), respectively. There were no significant differences in TNF-α, ICAM-1, endothelial NOS and iNOS mRNA expression among the groups. Conclusion In rats with bacterial pneumonia, inhaled NO and /or low and high levels of oxygen exerte different modulatory effects on pulmonary cNOS and iNOS activity and levels of TNF-α and ICAM-1, which may account for mechanisms of mitigating of inflammatory lung injury.

关 键 词：炎症介质 细菌性肺炎 肿瘤坏死因子α(TNF-α) NOS活性 ICAM-1表达 克雷白杆菌肺炎 肺炎克雷白杆菌 细胞间黏附分子 吸入一氧化氮 mRNA表达 iNOS 内皮细胞型 肺组织 正常对照 健康大鼠 NO合酶 蛋白水平 表达差异 调节作用 

分 类 号：R563.1[医药卫生—呼吸系统]