核因子-κB在小鼠急性肺损伤发病中的作用及治疗干预研究  

Role of nuclear factor-kappa B activation in mice with acute lung injury induced by lipopolysaccharide

作　　者：杨毅[1] 邱海波[1] 周韶霞[1] 许红阳[1] 刘少华[1] 郑瑞强[1] 黄英姿[1] 

机构地区：[1]东南大学附属中大医院ICU

出　　处：《中国急救医学》2003年第2期63-66,共4页Chinese Journal of Critical Care Medicine

基　　金：江苏省青年基金 (BQ980 35 );铁道部科学基金 (J98Z0 2 6 );东南大学科学基金 ( 92 47341174;0 0 -xy -35 )

摘　　要：目的　探讨核因子 (NF) -κB在内毒素 (LPS)诱导的急性肺损伤 (ALI)小鼠发病中的作用以及地塞米松 (Dex)的干预作用。方法　腹腔内注射LPS诱导小鼠ALI模型 ,随机分为LPS组、LPS +Dex组 ,LPS注射后 0、1、3、6、12h测定肺湿重 干重比值 (W D)、肺组织NF -κB活性、肺组织匀浆中肿瘤坏死因子 (TNF)α及白细胞介素 (IL) - 10浓度 ,检测mRNA表达 ,并观察肺组织光镜、电镜病理改变。结果　LPS注射后 ,W D明显增高 ,3h开始明显升高 ,6h达到高峰 ( 4 82± 0 10 ) ,显著高于注射前 ( 3 6 7± 1 0 4,P <0 0 5 ) ;肺组织核蛋白NF -κB活性 1h开始明显升高 ,6h达到峰值 ( 40 5 7± 6 2 4) ,显著高于注射前( 44 8± 30 9,P <0 0 5 ) ;肺组织匀浆TNF -α和IL - 10浓度分别在注射后 6h和 12h升高最明显 ,分别为 ( 197 1± 5 2 4)pg mL和 ( 16 4 9± 39 7)pg mL ,显著高于注射前。地塞米松明显抑制NF -κB活化 ,肺组织匀浆中TNF -α、IL - 10及其mRNA表达明显下降。肺组织病理显示LPS可导致肺泡出血、水肿 ,大量炎症细胞浸润 ,电镜下见Ⅰ型肺泡上皮细胞断裂 ,Ⅱ型肺泡上皮细胞变性 ,地塞米松可明显改善肺损伤。结论　LPS导致肺组织NF -κB的活化 ,介导炎症介质大量表达 ,参与ALI发生 ,地塞米松通过抑制炎症反?Objective To investigate the potential role of nuclear factor kappa B (NF-κB) activation and Dexamethasone (Dex) in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods All mice were randomly divided into two groups (LPS group, LPS+Dex group). At 0, 1, 3, 6 and 12 h after LPS injection,lung wet/dry weight (W/D) was recorded to assess lung injury. The total lung homogenates were prepared to detect NF-κB activation, tumor necrosis factor(TNF)-α and interleukin (IL)-10 levels and their mRNA expression. Meanwhile, pathological changes were examined under optical and electronic microscope. Results After LPS injection, W/D increased obviously at 3 h and peaked at 6 h(4.82±0.10), and which was higher (compared with pre-LPS injection 3.67±1.04, P<0.05). NF-κB in lung homogenates raised markedly from(44.8±30.9) at 0 h to (405.7±62.4)at 6 h.The levels of TNF-α in lung homogenates were increased significantly at 6 h (197.1±52.4)pg/mL to compare with pre-LPS injection(61.2±10.7)pg/mL.IL-10 peaked at 12 h after LPS injection (164.9±39.7)pg/mL, which was higher 〔compared with pre-LPS injection(71.6±15.9)pg/mL〕. TNF-α and IL-10 and their mRNA levels in Dex group also decreased significantly. Histologically, massive alveolar edema, hemorrhage, and inflammatory cell infiltration were observed under optical microscope. Alveolar epithelial cell Ⅰ disrupted and alveolar epithelial cell Ⅱ degranulated under electronic microscope. But lung injury was improved at Dex group. Conclusions LPS could induce NF-κB activation and up-regulate inflammatory mediator expression in ALI mice. The activation of NF-κB and excessive expression of cytokines might play an important role in the pathogenesis of ALI.

关 键 词：核因子-KB 小鼠 急性肺损伤 发病 治疗 干预 研究 

分 类 号：R563.8[医药卫生—呼吸系统]