摘要
目的观察选择性一氧化氮合酶抑制剂氨基胍(aminogunidine,AG)对大鼠内毒素性肺损伤(acute lung injury,ALI)NF-κB相关信号通路和炎症反应的影响,探讨AG对肺损伤组织的保护作用及其机制。方法健康♂SD大鼠随机分为对照组、模型组和AG治疗组。模型组、AG治疗组静脉注射脂多糖(lipopolysaccharide,LPS)复制内毒素性肺损伤模型。各组按治疗时间又分为给LPS3h后治疗3h(3h+3h)组和给LPS6h后治疗3h(6h+3h)组,分别于给LPS3h和6h后腹腔注射生理盐水(对照组及LPS组)和AG(100mg.kg-1,AG治疗组)。每组8只动物。免疫组化染色分析肺组织中核因子-κB(NF-κB)的核移位和粘附分子-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,明显从细胞质移位于细胞核,表达量也明显增加;ICAM-1蛋白表达增加;肺组织中TNF-α、IL-6含量明显升高。肺损伤3h用AG治疗3h后,NF-κB从细胞质向细胞核的移位被明显限制,NF-κB的表达量、ICAM-1蛋白表达和肺组织中TNF-α、IL-6含量明显低于相应的LPS组,肺组织病理改变减轻;肺损伤6h用AG治疗3h后,治疗效果较差。结论AG于LPS3h后给药可减轻内毒素性肺损伤,可能与减弱诱导型一氧化氮合酶(iNOS)mRNA表达、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,下调炎症因子和ICAM-1的表达有关。
Aim To investigate the effect and the possible mechanism of aminoguanidine （AG） on the lipopolysaceharide （LPS）-induced acute lung injury in rats. Methods Male SD rats were randomly divided into control group, LPS group and AG group. AG was administered in AG group, saline was administered in control group and LPS group. All the groups were further divided into 2 subgroups according to the duration of ALI：3 h ＋ 3 h group and 6 h ＋ 3 h group. In AG group and LPS group, LPS was administered . Saline was administered in control group. The translocation of NF-KB and the expression of intercellular adhesion molecule-1 （ICAM-1） were respectively detected with immunohistoehemisty （ IHC ） ; the concentrations of TNF-α and IL-6 in lung tissue were evaluated by radioimmunoassay;the pathological changes of lung tissue were observed by light and electron microscope. Results Compared with those of the control group, NF- KB was significantly translocated from the cytoplasm into the nucleus, the expression of NF-KB and ICAM-1protein were significantly increased. The concentrations of TNF-α and IL-6 in lung tissue were significantly increased in LPS group. Degree of ALl was gradually worsened after administration of LPS. In AG （3 h ＋ 3 h） group,the expression of NF-KB and ICAM-I protein were significantly decreased, the concentrations of TNF-α and IL-6 in lung tissue were significantly decreased and the lung damage was improved compared with those of the LPS（3 h ＋ 3 h） group. Conclusions Administration of AG could ameliorate LPS-induced acute lung injury in rats. The possible mechanism was that AG could reduce the expression of iNOS mRNA,inhibited NF-KB activation and subsequently led to the down-regulation of NF-KB-dependent inflammatory gene expression and thus reduced the inflammatory response in lung injury.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2008年第11期1492-1495,共4页
Chinese Pharmacological Bulletin
基金
国家人事部留学人员重点资助项目(No9900789)
河北省博士基金资助项目(No995470151)
