家兔呼吸机所致肺损伤HSP70与I-κBα表达的意义

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

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。

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 （VT = 10 mL·kg^-1, group NVC）, ventilated normally all the time, injured ventilation ＋ 3 cm H2O PEEP（ VT = 40 mL·kg^-1 , PEEP = 3 cm H2O, group PEEP） and injured ventilation ＋ 0 cm H20 PEEP（VT = 40 mL·kg^-1, PEEP = 0 cm H2O, 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.