摘要
目的 探讨大鼠机械通气所致呼吸机相关性肺损伤（VILI）时p38丝裂原活化蛋白激酶（MAPK）的激活以及致炎因子的表达。方法 30只健康SD大鼠随机均分成A、B、C3组，A组：潮气量（VT）8ml／kg，呼吸频率（RR）80次／min；B组：VT20ml／kg，RR80次／min；C组：VT40ml／kg，RR80次／min。各组机械通气时间均为2h。实验结束处死大鼠，收集支气管肺泡灌洗液（BALF）和肺组织标本，光镜下观察肺组织病理学改变。采用蛋白质免疫印迹法（Western blotting）检测各组肺组织中p38、磷酸化P38（p—p38）水平，逆转录-聚合酶链反应（RT—PCR）检测细胞间黏附分子-1（ICAM-1）表达水平，考马斯亮蓝染色法检测肺组织中总蛋白浓度和髓过氧化物酶（MPO）活性，双抗体夹心酶联免疫吸附法检测BALF中肿瘤坏死因子-α（TNF—α）、巨噬细胞炎症蛋白-2（MIP-2）和白细胞计数（WBC）。结果 肺组织病理观察显示，A、B、C3组的改变依次加重：与A组相比．B、C两组p～p38和ICAM-1的表达以及总蛋白、WBC、MIP-2、TNF—α及MPO的水平均显著增高（P均〈0．01）；与B组相比，C组p—p38和ICAM-1的表达以及总蛋白、WBC、MIP-2、TNF—α及MPO的水平均显著增高（P〈0．05或P〈0．01）。结论 大VT机械通气能显著激活p38通路以及致炎因子的表达，这可能是大鼠机械通气所致肺损伤的重要致病机制之一。
Objective To study the activation of p38 mitogen -activated protein kinase （MAPK） and the expression of inflammatory cytokines in ventilator -induced lung injury （VILI） in rat. Methods Thirty healthy male SD rats were randomly divided into three group （A, B, C group, n= 10 per group）. Mechanical ventilation was instituted in all the groups. A group： tidal volume （VT）= 8 ml/kg, respiratory rate （RR）=80/min; B group.. VT=20 ml/kg, RR=80/min; C group： VT=40ml/kg, RR=80/min. The time of ventilation for all the groups was two hours. Rats were sacrificed after experiment was finished. The bronchial lavage liquid and lung tissue were collected and stored with routine methods. The pathological changes in lung tissue were examined with optical microscope. The expression of p38 and phos -p38 （p-p38） were measured by Western blotting in lung tissues. The expression of intercellular adhesion molecular- 1 （ICAM -1 ） was detected by reverse transcriptase- polymerase chain reaction （RT- PCR）. The contents of total protein, white blood cells （WBC）, myeloperoxidase （MPO）, macrophage inflammatory protein - 2 （MIP - 2） and tumor necrosis factor - α （TNF - α） were also determined. Results Compared with A group, total protein, WBC, MPO, MIP-2, TNF-α, ICAM - 1 and p -p38 were significantly increased in B group and C group （all P〈0.01）. Compared with B group, the above indexes were also significantly increased in C group （P〈0.05 or P〈0.01）. Conclusion Large VT mechanical ventilation can significantly activate the p -p38 and inflammatory cytokines, which may play an important role in VILI.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2007年第2期77-80,I0001,共5页
Chinese Critical Care Medicine
基金
国家自然科学基金资助项目（30571787）
湖北省科技攻关计划（2005AA301C23）
