摘要
目的 探讨机械通气对大鼠肺泡巨噬细胞（AM）表面Toll样受体4（TLR4）表达的影响。方法 清洁级成年雄性SD大鼠18只，随机分为自主呼吸组（R组，n=6）、小潮气量（VT）机械通气组（M组，n=6）和大VT机械通气组（N组，n=6）。腹腔注射质量分数为20％的乌拉坦8mg／kg麻醉大鼠，行气管插管。机械通气呼吸机参数设定：M组：VT为6ml／kg，N组VT为40ml／kg，吸：呼为1：1，呼气末正压（PEEP）为0，吸入氧浓度（FiO2）为0．21。调整呼吸频率和潮气末二氧化碳分压（PETCO2）维持在35～45mmHg（1mmHg=0．133kPa）。实验3h结束，放血处死大鼠。监测实验开始及实验1、2和3h时动脉血气分析；并测定大鼠肺组织病理形态学积分、湿／干重（W／D）比值及支气管肺泡灌洗液（BALF）中自细胞计数（WBC）和肺蛋白通透性系数。用逆转录-聚合酶链反应（RT—PCR）测定AM表面的TLR4mRNA表达，用免疫组化法测定AM表面的TLR4蛋白表达。结果 N组实验1h时存在过度通气，pH升高、动脉血二氧化碳分压（PaCO2）降低（P均〈0．05），其他指标都在正常范围内。与R组比较，N组肺组织病理形态学积分、W／D比值，BALF中WBC和肺蛋白透性系数以及TLR4蛋白表达和TLR4mRNA表达均显著升高（P均〈0．01）；M组改变差异均无显著性（P均〉0．05）。结论 大VT机械通气导致大鼠肺损伤，并使AM表面TLR4表达明显上调。小VT机械通气可避免上述改变的发生。
Objective To investigate the effects of mechanical ventilation on Toll like receptor 4 （TLR4） in rat＇s alveolar macrophages （AM）. Methods Eighteen depuratory -class adult male SD rats weighting 230- 240 g were randomly divided into three groups （n = 6）： autonomous breathing group （R group）, small tidal volume （VT） mechanical ventilation group （M group, VT= 6 ml/kg） and large VT mechanical ventilation group （N group, VT=40 ml/kg）. The animals were anesthetized with intraperitoneal 20% urethane 8 ml/kg, tracheostomized and mechanically ventilated （inhalation ： exhalation （I ： E）= 1 ： 1, with positive end - expiratory pressure （PEEP） = 0, fraction of inspired oxygen （FiO2） = 0.21]. The respiratory rate was adjusted, and end- tidal carbon dioxide partial pressure （PETCO2） was maintained at 35- 45 mm Hg （1 mm Hg= 0. 133 kPa）. Arterial blood samples were taken for blood gas analysis at the beginning of the experiment and 1, 2 and 3 hours after the experiment. The experiment was terminated, and pathomorphology score, pulmonary tissue wet/dry （W/D） weight ratio, white blood cells count （WBC） in bronchoalveolar lavage fluid （BALF） were determined at 3 hours. The rats were sacrificed by bloodletting after experiment. Then the rats＇ BALF and pulmonary albumin permeability （PAP） were determined. The expression of AM TLR4 mRNA was assessed by semi -quantitative reverse transcription -polymerase chain reaction （RT- PCR）. AM TLR4 protein expression was determined by immunohistochemistry. Results Over ventilation, elevated pH and lower partial pressure of carbon dioxide in arterial blood （PaCO2） were observed in N group at 1 hour, and other indexes were normal. The pulmonary pathomorphology score, pulmonary W/D weight ratio, WBC in BALF, PAP, and the mRNA expression of TLR4 and the protein of TLR4 in AM in the N group were greatly increased as compared with the R group （all P〈0. 01）, while they were not significantly changed in the M group （all P〉0. 05）. Conclusion Large VT mechanical ventilation induced injury of lungs and up - regulated TLR4 expression in rat＇s AM. Small VT mechanical ventilation avoided above -mentioned changes.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2007年第2期73-76,I0001,共5页
Chinese Critical Care Medicine
基金
国家自然科学基金资助项目（30471661）
山东省自然基金资助项目（Y2006C120）
关键词
机械通气
肺损伤
TOLL样受体4
肺泡巨噬细胞
mechanical ventilation
injury of lungs
Toll like receptor 4
alveolar macrophages
