吸入不同浓度一氧化氮对急性肺损伤小鼠肺组织炎症反应的影响  

Effect of different concentration of nitric oxide on pulmonary inflammatory response in mice 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：《江苏医药》2004年第12期894-897,共4页Jiangsu Medical Journal

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

摘　　要：目的　探讨吸入一氧化氮 (NO)对急性肺损伤 (ALI)小鼠肺组织炎症反应的影响。方法　脂多糖 (LPS)腹腔注射诱导小鼠ALI模型 ,吸入不同浓度NO ,测定肺组织核因子 (NF) κB活性及肿瘤坏死因子 (TNF)α、白介素 (IL) 1 0mRNA的表达。结果　与LPS组 (A组 )比较 ,LPS +吸入NO 5 ppm(B组 )、LPS +吸入NO 2 0 ppm(C组 ) 1 2小时湿重 /干重 (W /D)显著降低 ,LPS +吸入NO4 0ppm(D组 )无明显差异。LPS注射后肺组织NF κB活性明显增强 ,6小时达到峰值 4 0 6± 6 2 ,显著高于LPS注射前 (45± 31 ,P <0 0 5 )。吸入NO 5 ppm和 2 0 ppm 6小时后 ,NF κB活性明显低于LPS组 (P <0 0 5 )。但吸入 4 0ppmNF κB活性在 3小时、6小时明显下降后 ,1 2小时又明显升高。B组和C组肺组织TNF α和IL 1 0浓度及mRNA表达在 3～ 1 2小时均明显降低 ,但D组吸入NO 4 0 ppm1 2小时 ,TNF α表达与LPS组无显著差异。吸入NO后各组IL 1 0表达均降低。结论　吸入 5 ppm和 2 0ppmNO可抑制LPS介导的NF κB活化 ,下调炎症因子表达 ,改善ALI ,但吸入 4 0 ppmNO加重肺损伤。Objective To investigate the effect of inhaled nitric oxide(NO)on pulmonary inflammatory response in mice with acute lung injury(ALI)induced by lipopolysaccharide(PLS). Methods ALI murine model was induced by intraperitoneal injection of LPS and then randomly assigned to four groups(LPS,LPS+inhaled NO5,20,40 ppm).Lung wet/dry weight ratios(W/D) were recorded to assess lung injury.The lung homogenates were prepared to detect NF-κB activity by electrophoretic mobility gel shift assay(EMSA),tumor necrosis factor(TNF)α and interleukin(IL)-10 levels by ELISA and their mRNA expression by RT-PCR.Results After LPS injection,W/D and NF-κB activity increased significantly.Compared to PLS group,W/D ratio decreased significantly in inhaled NO 5,20 ppm group at 12 h after LPS exposure,but in NO 40 ppm group,the ratio decreased at 3 h and raised again at 12 h.NF-κB activity in lung homogenates in LPS group was 405.7±62.4 at 6 h,which decreased significantly to 288.9±36.3 and 250.6±51.5 respectively in NO 5 ppm and 20 ppm group.In NO 40 ppm group,NF-κB activity was decreased at 3 h and 6 h as compared with that in LPS group,but increased to 338.2±65.4 significantly.Compared with LPS group,TNF-α and IL-10 levels and their mRNA levels in lung homogenates were decreased at 3h,6h and 12h in NO 5 ppm and 20 ppm group.In NO 40 ppm group,TNF-α and IL-10 levels and their mRNA levels were decreased at 3 h and 6 h,but increased at 12 h.Conclusion NO inhalation decreased NF-κB activation and down-regulated inflammatory mediator expression in ALI mice.But high level NO(40 ppm)might have deleterious effect on lung injury.

关 键 词：吸入 LPS 肺组织 小鼠 NF-KB 炎症反应 ALI 活性 增强 降低 

分 类 号：R563[医药卫生—呼吸系统] R725[医药卫生—内科学]