EGFR在大鼠呼吸机肺损伤中的作用研究

目的研究呼吸机所致肺损伤中表皮生长因子受体(EGFR)的激活作用。方法 24只清洁级雄性SD大鼠按照是否AG1478处理和是否机械通气将其分为DMSO自主呼吸组(n=6)、DMSO机械通气组(n=6)、AG1478 10mg/kg处理自主呼吸组(n=3)、AG1478 50mg/kg处理自主呼吸组(n=3)、AG1478 10mg/kg处理机械通气组(n=3)和AG1478 50mg/kg处理机械通气组(n=3)。20%乌拉坦腹腔注射麻醉大鼠;自主呼吸的大鼠不作处理,机械通气的大鼠接小动物呼吸机行机械通气,机械通气参数设置为潮气量(Vt)20ml/kg,呼吸频率40次/min,吸呼比(I∶E)为1∶2,呼气末正压通气(PEEP)为0,吸入气体为室内空气。皮下切开行股静脉穿刺置管,监测动脉血压、心率等。4h后处死,分别收集肺组织、肺灌洗液标本。结果 AG1478 50mg/kg处理机械通气组与DMSO机械通气组相比蛋白渗漏更低,而且比AG1478 10mg/kg机械通气更低,差异均有统计学意义(P<0.05);细胞数量分析显示,AG147850mg/kg处理机械通气组与DMSO机械通气组相比中性粒细胞更低,而且比AG1478 10mg/kg处理自主呼吸组更低,差异均有统计学意义(P<0.01);AG1478 50mg/kg处理的大鼠巨噬细胞数量显著升高,均高于其他处理手段的大鼠。同样行机械通气的大鼠,AG1478组的肺血管渗漏水平与DMSO组相比更低。结论呼吸机相关肺损伤中,EGFR路径调节呼吸机诱导的肺损伤和与之相关的炎性反应,EGFR具有活化信号的作用,可调节呼吸机诱导的肺血管渗漏。

The effect of EGFR on ventilator-induced lung injury in rats

Objective To study the activation effect of EGFR on ventilator-induced lung injury.Methods 24 clean male SD rats according to whether AG1478 processing and mechanical ventilation divided to spontaneous respiratory with DMSO treatment group（n=6）,mechanical ventilation with DMSO treatment group,spontaneous respiratory with AG1478 10 mg/kg treatment group,mechanical ventilation with AG1478 10 mg/kg treatment group,spontaneous respiratory with AG1478 50 mg/kg treatment group and mechanical ventilation with AG1478 50 mg/kg treatment group.The rats anesthetized by intraperitoneal injection of 20% urethane.The rats of spontaneous respiration without and the rats of mechanical ventilation with small animal respirator,Mechanical ventilation parameter settings for the tidal volume（Vt） 20 ml/kg,40/min,respiratory rate,breath ratio（I∶E） of 1∶2,positive end expiratory pressure（PEEP）0,Inhalation gases was indoor air.Subcutaneous incision for femoral vein puncture,monitoring of arterial blood pressure,heart rate and other.Collected respectively,lung tissue,lung lavage fluid specimens after put to death.Results Mechanical ventilation with AG1478 50 mg/kg treatment group protein leakage is lower compared with mechanical ventilation with DMSO treatment group,and lower than mechanical ventilation with AG1478 50 mg/kg treatment group;Cell number analysis showed that the number of neutrophils in BAL fluid in mechanical ventilation with AG1478 50 mg/kg treatment group was significantly lower than mechanical ventilation with DMSO treatment group,also compared with mechanical ventilation with AG1478 10 mg/kg treatment group.Macrophage numbers increased significantly in mechanical ventilation with AG1478 50 mg/kg treatment group.The pulmonary vascular leakage levels of AG1478 group was lower than DMSO group.Conclusion For ventilator-induced lung injury,EGFR path adjusting ventilator induced lung injury and the associated inflammatory reaction,EGFR has activation signal function,can adjust the ventilator induced lung vascular leakage.