呼吸机相关肺损伤兔细胞间黏附分子-1和白细胞介素-10的表达及激活蛋白-1活性的变化  

Expression of intercelluler cell adhesion molecule-1, interleukin-10 and the activation of activator protein-1 in ventilator-induced lung injury in rabbits

作　　者：张隽[1] 童朝晖[1] 秦志强[1] 庞宝森[1] 牛淑洁[1] 王辰[1] 

机构地区：[1]首都医科大学附属北京朝阳医院-北京呼吸疾病研究所,100020

出　　处：《中华结核和呼吸杂志》2010年第8期587-592,共6页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的 研究呼吸机相关肺损伤（VILI）兔细胞间黏附分子-1（ICAM-1）、白细胞介素（IL）-10的表达及激活蛋白-1（AP-1）DNA结合活性的变化,并探讨其在VILI炎症反应中的意义.方法 应用40 ml/kg的大潮气量（VT）机械通气建立兔VILI模型.将40只新西兰兔按随机数字表法分为非机械通气对照组、常规VT组、大VT 1h组、大VT 2 h组及大VT 4 h组.用酶联免疫吸附法（ELISA）检测肺组织匀浆可溶性细胞间黏附分子-1（sICAM-1）和IL-10含量,逆转录多聚酶链反应（RT-PCR）检测mRNA表达.凝胶电泳迁移率分析法（EMSA）测定AP-1的活性,同时测定PaO2、髓过氧化物酶（MPO）、肺湿重/干重比值（W/D）.结果 （1）肺组织匀浆中sICAM-1含量：大VT2 h组[（23±5）ng/L]及大VT 4 h组[（35±5）ng/L]均高于常规VT组[（16±4）ng/L],均P＜0.05;大VT4 h组高于大VT 1 h组[（19±4）ng/L]及大VT 2 h组（均P＜0.01）.肺组织匀浆IL-10含量：大VT2 h组[（24±4）ng/L]和大VT4 h组[（26±5）ng/L]均高于常规VT组[（15±2）ng/L,均P＜0.05],大VT4 h组高于大VT 1 h组[（19±4）ng/L,P＜0.05].ICAM-1 mRNA含量：大VT 2 h组（1.18±0.19）及大VT4 h组（1.29±0.19）均高于常规VT组（0.84±0.13,均P＜0.05）.大VT4 h组高于大VT1 h组（0.96±0.24,P＜0.05）.IL-10 mRNA含量：大VT 4 h组（1.13±0.17）高于常规VT组（0.84±0.20）和大VT 1 h组（0.86±0.12,均P＜0.05）.（2）AP-1的DNA结合活性：大VT 2 h组（34±8）和大VT4 h组（38±9）均高于常规VT组（23±9,均P＜0.01）,大VT4 h组高于大VT 1 h组（25±9,P＜0.01）.（3）病理学检查显示大VT机械通气后随时间延长肺损伤逐渐加重,大VT机械通气2 h可见MPO升高,4 h可见PaO2下降及W/D升高.结论 ICAM-1、IL-10参与了VILI的炎症反应过程,二者升高可能与其mRNA的表达增高有关.核转录因子AP-1可能参与了上述炎性介质基因的转录调节.Objective To study the expression of intercelluler cell adhesion molecule-1 （ICAM-1） , Interleukin-10（1L-10）and the activation of transcription factor activator protein-1 （AP-1 ）in a rabbit model of ventilator-induced lung injury （ VILJ） and therefore to explore their possible role in VILI. Methods The VILI model was established by mechanical ventilation with a large tide volum （VT ） of 40 ml/kg. Forty healthy male New Zealand rabbits were randomly divided into 5 groups： a control group without mechanical ventilation, a conventional ventilation group, and injurious ventilation with large VT for 1 h group, 2 h group and 4 h group. The concentrations of soluble ICAM-1 （ sICAM-1 ） and IL-10 in lung homogenates were measured by enzyme-linked immunosorbent assay （ ELISA） . The level of mRNA was measured by semiquantitative transcription-polymerase chain reaction （ RT-PCR）. The DNA-binding activity of AP-1 was measured by electrophoretic mobility shift assay （ EMSA）. The partial arterial blood pressure of oxygen （PaO2） , myeloperoxidase （MPO） in lung homogenate, wet lung weight to dry lung weight ratio （W/D） were observed. Results （l）The concentrations of sICAM-1 in large VT for 2 h group （23 ±5） ng/L and 4 h group（35 ±5） ng/L were higher than that in the conventional ventilation group（ 16 ±4）ng/L（P all 〈 0. 05） ,and that in the Large VT for 4 h group were higher than that in 1 h group（19 ±4）ng/L and 2 h group （P all 〈 0.01）. The concentrations of IL-10 in the large VT for 2 h group （24 ±4） ng/L and 4 h group（26 ±5） ng/L were higher than that in the conventional ventilation group（15 ±2）ng/L（P all 〈0. 05） , and that in the Large VT for 4 h group was higher than that in the 1h group（ 19 ±4）ng/L（P 〈0.05）. The level of ICAM-1 mRNA in the large VT for 2 h group （1. 18 ± 0. 19） and 4 h group （1. 29 ±0. 19） were higher than that in the conventional ventilation group （0. 84±0. 13）（Pall〈0. 05�

关 键 词：呼吸 人工 呼吸窘迫综合征 成人 转录因子AP-1 细胞黏附分子 白细胞介素10 

分 类 号：R563.8[医药卫生—呼吸系统]