丙泊酚对呼吸机所致肺损伤大鼠的保护作用及其机制  

Mechanistic study of the protective effects of propofol on a rat model of ventilator-induced lung injury

作　　者：程傲冰[1] 丁宁[1] 许立新[1] 佘守章[1] 

机构地区：[1]广州市第一人民医院麻醉科,广东广州510180

出　　处：《热带医学杂志》2012年第7期799-802,共4页Journal of Tropical Medicine

基　　金：广东省科技计划项目(2010B031600011);广东省医学科研基金(A2009497);广州市科技计划项目(12C23151641);广州市医药卫生科技项目(20121A011026;20121A021001)

摘　　要：目的探讨p38信号通路在丙泊酚抑制呼吸机所致肺损伤(VILI)大鼠肺组织表达高迁移率族蛋白B1(HMGB1)中的作用。方法将32只健康SD大鼠随机分为4组,每组8只。对照组(A组)不行机械通气,保留自主呼吸;常规通气组(B组)潮气量(VT)为8ml/kg;大潮气量通气组(C组)VT为30ml/kg;大潮气量通气+丙泊酚组(D组)VT为30ml/kg,同时静脉注射丙泊酚8mg/(kg.h)。机械通气4h后处死动物,测定支气管肺泡灌洗液(BALF)中总蛋白水平、白细胞计数以及肺湿干重比值(W/D)和中性粒细胞髓过氧化物酶(MPO)活性。采用Western blot方法检测肺组织HMGB1蛋白含量以及p38的激酶活性,采用RT-PCR方法检测HMGB1 mRNA的表达。应用单因素方差分析进行不同组别间的比较。结果通气4h后,与A组相比,C组总蛋白水平(1.58±0.46)g/L、白细胞计数(112.05±21.33)×107/L、肺W/D比值(8.25±0.92)、MPO活性(3.08±0.85)U/g、HMGB1蛋白(0.43±0.13)和mRNA(0.30±0.08)表达以及p38激酶活性(0.52±0.11)均明显增加(P<0.05);与C组相比,D组上述各项指标的变化均明显降低(P<0.05)。结论丙泊酚可改善VILI肺内炎症反应,可能与通过p38信号通路抑制HMGB1蛋白和mRNA的表达有关。Objective To investigate the role of p38 MAPK pathway in propofol-induced inhibition of high mobility group box 1 （HMGB1） expression in lung tissue in a rat model of ventilator-induced lung injury. Methods Thirty-two healthy Sprague Dawley （SD） rats were randomly divided into 4 groups （n=8 each）： group A, spontaneous breathing; group B, small tidal volume ventilation （VT=8 ml/kg）, group C, high tidal volume ventilation （VT=30 ml/kg） and group D, high tidal volume ventilation （VT=30 mlfkg） with intravenous administration of propofol 8 mg/（kg, h）. The animals were mechanically ventilated for 4 h and then all animals were sacrificed. The lungs were removed for： （ 1 ） lung lavage, determination of total protein content, and WBC and neutrophil counts in broncho-alveolar lavage fluid （BALF） ; （2） determination of W/D lung weight ratio and myeloperoxidase （MPO） activity; （3） determination of HMGB1 protein and mRNA expression and p38 MAPK activity in lung tissue. Results The inflammatory response, as evidenced by total protein （1.58±0.46）g/L and WBC （112.05±21.33）× 107/L in BALF, W/D lung weight ratio （8.25±0.92） and MPO activity （3.08±0.85）U/g were significantly higher in group C compared with group A （P〈0.05） ; The expressions of HMGB1 protein （0.43±0.13） and mRNA （0.30±0.08）, and p38 activity （0.52±0.11 ） were also significantly increased in group C （P〈0.05）. The above indexes in group D were significantly lower than the group C （P〈0.05）. Conclusion Propofol attenuated high tidal volume ventilation-induced acute lung injury, which may be related to the downregulation of HMGB1 protein and mRNA expression through p38 MAPK signal pathway.

关 键 词：丙泊酚 机械通气 急性肺损伤 高迁移率族蛋白B1 P38丝裂原活化蛋白激酶 

分 类 号：R563.9[医药卫生—呼吸系统]