呼吸机所致肺损伤家兔HSP70和NF-κB表达的意义

Expression of heat shock protein 70 and nuclear factor-κB in ventilator-induced lung injury in rabbit

目的研究呼吸机所致肺损伤(VILI)炎症反应中热休克蛋白70(HSP70)和核因子-κB(NF-κB)表达的意义,以及加用呼气末正压(PEEP)的影响。方法健康成年新西兰白兔30只,实施麻醉和气管切开术后分别接受不同潮气量(VT)的通气(通气时间均为4h)。随机分为以下三组PEEP组(VT=40ml/kg,PEEP=3cmH2O,n=12);ZEEP组(VT=40ml/kg,PEEP=0cmH2O,n=12);对照组(VT=10ml/kg,n=6),始终以正常条件通气。机械通气开始后4h经颈动脉放血处死动物。在光镜下观察肺组织的病理学改变,Westernblot检测家兔肺组织HSP70及NF-κB的表达。结果家兔在致伤机械通气4h后,光镜下可见肺组织有不同程度的损伤;各组肺组织HSP70、NF-κB表达均显著增加,且ZEEP组二者呈负相关。与ZEEP组比较,PEEP组肺组织的病理损伤明显减轻,NF-κB表达明显减少。结论HSP70可通过抑制NF-κB的活性,保护肺组织避免VILI;在机械通气过程中加用PEEP也可通过减少NF-κB的表达减轻肺组织损伤。

Objective To investigate heat shock protein 70 （HSP70） and nuclear factor-kappa B（ NF-kB） expression in the lung after mechanical ventilation with PEEP（positive end expiratory pressure）in a rabbit model of ventilator-indueed lung injury （VILI）. Methods Thirty healthy adult white rabbits were randomly divided into three groups. After anesthesia and tracheostomy were installed, rabbits received ventilation with different tidal volumes for 4 hrs. In PEEP group, rabbits received ventilation withVT = 40ml/kg, PEEP = 3emH2O; group, rabbits received ventilation with VT=40ml/kg, PEEP=0cmH2O; and NVC group, with normal ventilation with VT= 10ml/kg. The different modalities of ventilation were maintained for 4 hours. After 4 hours, rabbits were killed by exsanguination, Lung histopathology was examined and compared among three groups. Expression of HSP70 and NF-kB were determined by using Western-blot technique. Results There were marked pathological changes in the lung tissue in group ZEEP, but pathological changes were relatively milder in group PEEP. After injurious ventilation for 4 hours, there was a significantly higher expression of HSP70 and NF-kB in group ZEEP, while that of NF-kB was negatively correlated with HSP70 levels. There was a significant lower expression of NF-kB in the lung of group PEEP,Conclusion We postulate that HSP70 expression protects the lung against ventilator-induced lung injury by down-regulating expression of NF-kB in the lung. Mechanical ventilation with PEEP can protect the lung against ventilator-induced lung injury through down-regulation of NF-kB in the lung.