NG-硝基-L-精氨酸对脂多糖诱导大鼠肺损伤炎症反应和核因子-κB信号通路的影响  

Effect of NG - nitro - L - arginine on inflammntory reaction and nuclear factor - κB signal pathway in the acute lung injury in rats induced by LPS

作　　者：李立萍[1] 张建新[1] 李兰芳[1] 解丽君[1] 张勤增[1] 郝娜[1] 李国风[1] 

机构地区：[1]河北省医学科学院药物研究所,石家庄050021

出　　处：《中国急救医学》2010年第6期517-520,共4页Chinese Journal of Critical Care Medicine

基　　金：国家人事部留学人员重点资助项目（No.9900789）;河北省博士基金资助项目（No.99547015D）

摘　　要：目的 观察非选择性一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸（NG-nitro-L-arginine, L-NA）对脂多糖诱导大鼠肺损伤炎症反应和核因子-κB（NF-κB）信号通路的影响.探讨L-NA对肺组织损伤的保护作用及其机制.方法 健康雄性SD大鼠随机分为正常对照组、模型组（LPS组）和L-NA治疗组（L-NA组）.模型组和L-NA组静脉注射脂多糖（LPS）5 mg/kg复制内毒素性肺损伤模型,3 h和6 h后腹腔注射L-NA（L-NA组）和生理盐水（对照组及LPS组）,治疗3 h.免疫组化染色分析肺组织中核因子-κB（NF-κB）的核移位和肺组织细胞间黏附分子-1（ICAM-1）表达;放射免疫法分别测定肺组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的含量;光镜、电镜观察肺组织病理变化.结果 与对照组比较,大鼠肺损伤后NF-κB活化,明显从细胞浆移位于细胞核,表达量也显著增加;ICAM-1蛋白表达上调;肺组织中TNF-α、IL-6含量明显升高.肺损伤3 h用L-NA治疗3 h后, NF-κB从细胞浆向细胞核的移位被明显限制,NF-κB的表达量、肺组织中ICAM-1的表达明显低于相应的LPS组,肺组织病理改变减轻;但TNF-α、IL-6含量没有明显的变化,肺损伤6 h用L-NA治疗3 h对LPS引起的ICAM-1的表达和TNF-α、IL-6含量变化没有明显影响.结论 肺损伤3 h后给予L-NA可减轻内毒素性肺损伤、抑制核因子的活化,在一定程度上阻断NF-κB相关信号通路的传导是其机制之一.Objective To investigate the effects and the mechanisms of NG - nitro - L - arginine on pulmonary inflammatory cytokine expression and nuclear factor - κB signal pathway in a model of lipopolysaccharide （LPS） induced acute lung injury. Methods Models of Acute lung injury were induced by injection（iv） of lipopolysaccharide （LPS） （5 mg/kg） in male Sprague - Dawley （SD） rats. L - NA （ L - NA group） or saline（ control and LPS group） was administrated respectively at 3 h or 6 h after LPS injection, the treatment lasted for 3 h, and the rats were sacrificed at 6 h or 9 h after saline （control） or LPS injection. The translocation of NF - κB and the expression of intercellular adhesion molecule - 1 （ ICAM - 1 ） in lung tissue were respectively detected with （IHC）; the concentrations of TNF-α and IL- 6 in lung tissue were respectively evaluated by radioimmunoassay; the pathological changes of lung tissue were observed by light and electron microscope. Results Compared with that of the control group, NF - κB was significantly translocated from the cytoplasm into the nucleus, the expressions of NF - κB and ICAM - 1 protein were significantly increased, the concentrations of TNF - α and IL - 6 in lung tissue were significantly increased in LPS group respectively. Compared with LPS group, treatment with L - NA at 3 h after LPS significantly decreased the expression of NF - κB and ICAM - 1 protein. And the lung damage was alleviated in L - NA（3 h ＋3 h） group. The concentrations of TNF- α and IL- 6 in lung tissue showed no significant difference between LPS group and L - NA group. Conclusion Administration of L - NA at 3 h after LPS might protect lung from LPS - induced injury by inhibiting NF - κB activation subsequently inhibiting the NF - κB - mediated nuclear factor - κB signal pathway.

关 键 词：N^G-硝基-L-精氨酸 急性肺损伤 核因子-ΚB 细胞间黏附分子-1 炎症因子 脂多糖 

分 类 号：R532.14[医药卫生—内科学]