核因子-κB在小鼠急性肺损伤中的作用  

The role of nuclear factor kappa B activation in rats with acute lung injury

作　　者：邱海波[1] 杨毅[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,东南大学急诊与危重病医学研究所,南京210009

出　　处：《中华急诊医学杂志》2003年第1期15-17,共3页Chinese Journal of Emergency Medicine

基　　金：江苏省青年基金资助项目 (BQ980 3 5 ) ;铁道部科学基金资助项目 (J98Z0 2 6) ;东南大学科学基金资助项目(92 473 41174)

摘　　要：目的　探讨核因子 (NF) κB在内毒素 (LPS)诱导的急性肺损伤小鼠发病中的作用。方法　腹腔内注射LPS诱导小鼠急性肺损伤模型。LPS注射后 0、 1、 3、 6、 12测定肺湿重 /干重比值 (W/D) ,迁移率改变电泳法检测肺组织NF κB活性 ,同时酶联免疫吸附法测定肺组织匀浆中肿瘤坏死因子 (TNF) α、白介素 (IL) 10浓度 ,RT PCR检测mRNA表达。结果　LPS注射后 ,W/D比值明显增高 ,6h升高最明显 (4 82± 0 10 ) ,显著高于LPS注射前 (3 6 7± 1 0 4 ,P <0 0 5 )。LPS注射后肺组织核蛋白NF κB活性明显增强 ,6h达到峰值 (40 5 7± 6 2 4 ) ,显著高于LPS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LPS注射后 6h和 12h升高最明显 ,分别为 (197 1± 5 2 4 )pg/ml和 (6 4 9± 39 7)pg/ml,显著高于LPS注射前 [分别为 (6 1 2± 10 7)pg/ml和 (71 6± 15 9)pg/ml]。与LPS注射前比较 ,LPS注射后 3～ 12h ,肺组织匀浆TNF α和IL 10mRNA表达显著增高。肺组织病理显示肺泡出血、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。结论　LPS导致肺组织NF κB的活化 ,介导炎症介质大量表达 。Objective To investigate the potential role of nuclear factor kappa B (NF κB) activation in rats with acute lung injury(ALI) induced by lipopolysaccharide(LPS).Methods ALI murine model was induced by infusing LPS intraperitoneally.At 0h,1h,3h,6h,and 12h after LPS exposure,lung wet/dry weight ratios(W/D) was recorded to assess lung injury.The total lung homogenates were prepared to detect NF κB activity by EMSA,tumor necrosis factor(TNF) α and interleukin(IL) 10 levels by ELISA,and mRNA expression by RT PCR.Results After LPS injection,W/D was increased obviously at 3h(4 80±0 31)and peaked at 6h(4 82±0 10),which were higher than W/D at 0h(3 67±1 04).NF κB activity in lung homogenates increased markedly from(44 8±30 9)at 0h to(405 7±62 4)at 6h.The level of TNF α in lung homogenates increased significantly at 6h (197 1±52 4)pg/ml,compared with pre LPS injection(61 2±10 7 pg/ml).IL 10 peaked at 12h after LPS injection(164 9±39 7)pg/ml,which was higher than the level of IL 10 at pre LPS exposure(71 6±15 9)pg/ml.Compared with pre LPS level,TNF α and IL 10 mRNA expression in lung homogenates increased obviously at 3h to 12h after LPS injection.Histologically,massive alveolar edema,hemorrhage,and inflammatory cell infiltration were observed.Conclusion LPS could induce NF κB activation and up regulate inflammatory mediator expression in ALI rats.The activation of NF κB and increased expression of cytokines might play an important role in the pathogenesis of ALI.[

关 键 词：急性肺损伤 核因子-ΚB 细胞因子 内毒素 

分 类 号：R563.9[医药卫生—呼吸系统]