家兔呼吸机所致肺损伤HSP70与I-κBα表达的意义

目的:研究在呼吸机所致肺损伤(VILI)的炎症反应中热休克蛋白(HSP70)和核因子抑制蛋白α(I-κBα)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,随机分为3组,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。对照组(VT=10mL/kg,NVC组),始终以正常条件通气,致伤通气+3cm H2O PEEP(VT=40mL/kg,PEEP=3cm H2O,PEEP组),致伤通气+0cm H2O PEEP(VT=40mL/kg,PEEP=0cm H2O,ZEEP组)。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,并采用Western-blot法检测家兔肺组织HSP70及I-κBα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,肺组织HSP70表达显著增加,且与I-κBα的表达呈正相关,而在致伤机械通气的同时加用PEEP,肺组织的病理损伤明显减轻。结论:HSP70表达增加可能通过阻断I-κBα的降解抑制炎症反应,保护肺组织避免VILI,而在机械通气过程中加用PEEP可使家兔肺组织的病理损伤减轻。

Heat shock protein 70 expression in ventilator-induced lung injury in rabbit

Objective:To investigate heat shock protein 70(HSP70)and inhibitor-Kappa B-α(I-κBα)expression and the effect of mechanical ventilation with PEEP(positive end expiratory pressure)in a model of ventilator-induced lung injury(VILI).Method:Thirty healthy adult white rabbits were divided into three groups at random.After anesthesia was administered and tracheotomy was performed,Rabbits received ventilation of different tidal volume ventilation for 4 hrs,control group(V_T= 10 mL·kg-1,group NVC),ventilated normally all the time,injured ventilation +3 cm H_2O PEEP(V_T= 40 mL·kg-1,PEEP= 3 cm H_2O,group PEEP)and injured ventilation+ 0 cm H_2O PEEP(V_T= 40 mL·kg-1,PEEP= 0 cm H_2O,group ZEEP).All animals were subsequently ventilated for 4 hours.After 4 hours,rabbits were killed by exsanguination.Lung histopathology was assessed and compared among three groups.Expression of HSP70 and I-κBα were detected by using Western-blot methods.Result:There was significant histological changes in the lung tissue in group ZEEP,but histological changes were relatively minor in group PEEP.After injured ventilation for 4 hours.There was a significant higher expression of HSP70 in group ZEEP,But I-κBα was positively correlated with HSP70 levels.Conclusion:We propose that HSP70 expression protects the lung against ventilator-induced lung injury by inhibition of I-κBα degradation in the lung.Mechanical ventilation with PEEP can protect the lung against ventilator-induced lung injury.