肥胖因素对大鼠呼吸机相关性肺损伤的影响

Effect of obesity factor on ventilator-induced lung injury in rats

目的评价肥胖因素对大鼠呼吸机相关性肺损伤(VILI)的影响。方法清洁级雄性SD大鼠45只,6~8周龄,按照体重分为3组(n=15):正常体重对照组(C组)、正常体重VILI组(CV组)和肥胖VILI组(FV组)。C组和CV组体重为233~267 g,FV组体重为288~332 g。C组潮气量VT 10 ml/kg,CV组和FV组潮气量VT 40 ml/kg,通气频率40次/min,吸呼比1∶2,PEEP 0 mmHg,FiO221%,机械通气4 h,制备大鼠VILI模型。分别于气管插管前即刻和机械通气4 h时采集动脉血样行血气分析,记录PaO2;剩余血样收集血浆。机械通气4 h时采血后处死大鼠,分离两侧肺组织,收集支气管肺泡灌洗液(BALF)。采用ELISA法检测血浆瘦素浓度、血浆及BALF中TNF-α、IL-1β、IL-6的浓度。测定肺组织湿重/干重(W/D)比值,HE染色后观察肺组织病理结果并进行肺损伤评分,采用Western blot法检测肺组织NF-κB p65表达水平。结果与C组和CV组比较,FV组血浆瘦素浓度升高(P<0.01)。与C组比较,CV组和FV组机械通气4 h时血浆和BALF中TNF-α、IL-6和IL-1β浓度升高,PaO2降低,肺损伤评分和肺组织W/D比值升高,NF-κB p65表达上调(P<0.01)。与CV组比较,FV组机械通气4 h时血浆和BALF中TNF-α、IL-6和IL-1β浓度降低,PaO2升高,肺损伤评分和肺组织W/D比值降低,NF-κB p65表达下调(P<0.05)。结论肥胖因素可减轻大鼠VILI,其机制可能与血浆瘦素水平升高有关。

Objective To evaluate the obesity factor on ventilator-induced lung injury(VILI)in rats.Methods Forty-five clean-grade male Sprague-Dawley rats,aged 6-8 weeks,were divided into 3 groups(n=15 each)according to the body weight:normal weight control group(group C),normal weight VILI group(group CV)and obese VILI group(group FV).The body weight was 233-267 g in C and CV groups and 288-332 g in FV group.In group C,the tidal volume(VT)was 10 ml/kg.In CV and FV groups,the rats were ventilated for 4 h with the VT set at 40 ml/kg,respiratory rate 40 breaths/min,inspiratory/expiratory ratio 1∶2,PEEP 0 mmHg,and fraction of inspired oxygen 21%to establish the VILI model.The arterial blood samples were collected immediately before tracheal intubation and at 4 h of mechanical ventilation for blood gas analysis and PaO2 recording.The remaining blood samples were used for plasma collection.The rats were sacrificed after blood collection at 4 h of ventilation,and the bilateral lung tissues were isolated to collect the bronchoalveolar lavage fluid(BALF).The concentrations of leptin in plasma and tumor necrosis factor-alpha(TNF-α),interleukin-1beta(IL-1β)and interleukin-6(IL-6)in plasma and BALF were detected by enzyme-linked immunosorbent assay.The wet/dry weight(W/D)ratio of lung tissues was measured.The pathological changes of lung tissues were observed after HE staining,and the lung injury score was evaluated.The expression of NF-κB p65 in lung tissues was detected by Western blot.Results Compared with group C and group CV,the plasma leptin concentration was significantly increased in group FV(P<0.01).Compared with group C,the concentrations of TNF-α,IL-6 and IL-1β in plasma and BALF were significantly increased,PaO2 was decreased,the lung injury score and W/D ratio of lung tissues were increased,and NF-κB p65 expression was up-regulated at 4 h of ventilation in CV and FV groups(P<0.01).Compared with group CV,the concentrations of TNF-α,IL-6 and IL-1β in plasma and BALF were significantly decreased,PaO2 was increased,the lung injury score and W/D ratio of lung tissues were decreased,and NF-κB p65 expression was down-regulated at 4 h of ventilation in group FV(P<0.05).Conclusion Obesity factor can reduce VILI in rats,and the mechanism may be related to the increase in plasma leptin levels.