晚期炎症介质在双重打击致急性肺损伤小鼠中作用的实验研究  

Late - acting inflammation in double - hit induced acute lung injury mice

作　　者：郭凤梅[1] 施毅[1] 徐慧英[1] 丁晶晶[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)呼吸科,210002

出　　处：《中国急救医学》2009年第3期241-245,289,共6页Chinese Journal of Critical Care Medicine

基　　金：南京军区南京总医院科研基金（No.Z2008014）;江苏省医学重点人才基金（No.RZ2007113）

摘　　要：目的观察双重打击导致急性肺损伤（ALI）时肺组织中高迁移率族蛋白B1（HMGB1）随病程的浓度变化及其致炎作用。方法建立出血性休克后感染致ALI小鼠模型，观察病变过程中检测时间点肺组织HMGB1浓度、髓过氧化物酶（MPO）含量和肺泡膜通透性的变化，比较抗-HMGB1抗体干预治疗前后小鼠肺内MPO含量、肺泡膜通透性和肺组织病理学的改变。结果出血性休克后感染致ALI小鼠肺组织HMGB1浓度于模型建立后4h升高，16h达高峰，48h仍显著高于对照组。MPO水平于模型建立后4h达峰值[（95．0±5．6）U／g肺组织]。模型建立后4h肺内伊文兰显著升高，于16h达高峰[（33．3±2．3）g·mL^-1·g^-1肺组织]。应用抗-HMGB1抗体可以显著降低肺内MPO浓度[抗体应用前（95．0±5．6）U／g肺组织、抗体应用后（50．0±6．4）Pg·mL^-1·mg^-1肺组织]、减轻肺内伊文兰含量和肺组织病理损伤。结论HMGB1是介导双重打击导致的AU的重要迟发性炎症介质。Objective To observe the participation of high mobility group box 1 （ HMGB1 ） in the pathogenesis of acute lung injury （ALI ）caused by double - hit. Methods The study was carried out by mouse sepsis after hemorrhagic shock - primed ALI model. We measured HMGB1 and myeloperoxidase hmg concentration and lung leak at the designated time points. We then specific inhibited of HMGB1 activity , and examined the effects of anti - HMGB1. Results Administration of lipopolysaccharide to hemorrhagic shock resulted in HMGB1 an increase by 4 h, and increased further by 16 h. Myeloperoxidase also increased significantly at 4 h [ （95.0 ± 5.6） U/g of lung]. Sepsis after hemorrhagic shock resulted in the highest lung leak at 16h. Compared with the shock/LPS mice, blockade of HMGB1 prevented significantly myeloperoxidase [ （ 95.0 ±5.6） U/g of lung vs （ 50.0 ±6.4 ） U/g of lung] , lung leak was also diminished markedly. Conclusion HMGB1 plays a key role as a late mediator in sepsis after hemorrhagic shock- primed ALI.

关 键 词：高迁移率族蛋白1 双重打击 急性肺损伤 

分 类 号：R563[医药卫生—呼吸系统]