反比通气和PEEP对肺损伤TNF

【关键词】  急性病；肺/损伤;反比通气;正压呼吸;肿瘤坏死因子

    【Abstract】 AIM:  To investigate the effects of inverse ratio ventilation(IRV) and positive endexpiratory pressure(PEEP) on TNFα, IL8 and ET1 in oleic acidinduced lung injury. METHODS: Sixteen New Zealand rabbits were randomly divided into 2 groups, IRV group(n=8) and PEEP group (n=8). The IRV group were ventilated with a tidal volume(VT) of 12 mL/kg, respiratory rate of 30 breaths/min, I∶E=3∶1 and PEEP of 0 cmH2O; in PEEP group, VT was 10 mL/kg  and respiratory rate 40 breaths/min, I∶E=1∶2 and PEEP=20 cmH2O;  FiO2=0.5 in both groups. Mixed venous blood 3 mL was taken via right ercernal jugular vein respectively at 0, 30, 60, 90 and 120 min during ventilating. The animals were sacrificed by draining artery blood at the end of experiment. Right lung was cut off for wet/dry weighing and left was lavaged. Concentrations of TNFα, IL8 and ET1 in blood plasma and bronchoalveolar lavage fluid(BALF) were measured by radioimmune assay. RESULTS: Levels of TNFα，IL8 and ET1 in BALF in IRV group were higher than those in PEEP group (P<0.05). Serum levels of TNFα，IL8 and ET1 in both groups after 30 min ventilation were significantly higher than those at base points (P<0.05). Additionally, with the proceeding of ventilation, TNFα, ET1  and IL8 in both groups were increasing gradually (P<0.05). Levels of TNFα, IL8 and ET1 in serum in PEEP group were lower significantly than those in IRV group (P<0.05) at the similar time points. In IRV vs PEEP, the ratio of wet to dry lung (%) surging(79±1 vs 62±1, P<0.01). Levels of TNFα，IL8 and ET1 in BALF  were correlated with the ratio of wet to dry lung（r1=0.8972, r2=0.9518, r3=0.8978）. CONCLUSION:  Lung inflammatory response of acute lung injury may be  alleviated more effectively in the setting of PEEP than IRV.

    【Keywords】 acute disease; lung/injuries; inverse ratio ventilation; positive  pressure respivetion; tumornecrosisfactoralpha;  interleukin8; endothelin1

    【摘要】  目的： 探讨反比通气（IRV）和呼气末正压通气（PEEP）对油酸所致急性肺损伤肺泡灌洗液及外周血中TNFα,  IL8, ET1的影响. 方法： 将16只新西兰大白兔随机分为两组,每组8只. IRV组，呼吸频率30次/min，I∶E=3∶1，潮气量12 mL/kg，PEEP=0；PEEP组，呼吸频率40次/min，I∶E=1∶2，潮气量10 mL/kg，PEEP=20 cmH2O（1 cmH2O=0.098 kPa）. 两组均以容量控制通气. 吸氧浓度(FiO2)=0.5. 在0, 30, 60, 90及120 min由右颈外静脉导管采集混合静脉血各3 mL,放免法测定血浆及肺泡灌洗液中肿瘤坏死因子(TNFα)、白细胞介素8(IL8)、内皮素1（ET1）的含量. 实验结束后放血处死动物,右肺用于肺湿质量/干质量比率测定. 结果：  两组BALF中TNFα，IL8，ET1浓度，IRV组明显高于PEEP组(P均<0.05)；两组血清中TNFα，IL8，ET1浓度，在肺损伤后30 min均显著升高,明显高于肺损伤前(P<0.05). 各组随着时间延长，三种细胞因子逐渐增加. PEEP组三种细胞因子浓度均明显低于对应时间点的IRV组(P均<0.05)；PEEP组肺干质量占肺湿质量(62±1)%,显著低于IRV组的(79±1)%(P<0.01). BALF中三种因子含量也与肺水质量分数呈显著正相关（r1=0.8972, r2=0.9518, r3=0.8978）. 结论： PEEP比IRV能更好地减少急性肺损伤的肺部炎症反应.

    【关键词】 急性病；肺/损伤;反比通气;正压呼吸;肿瘤坏死因子α; 白细胞介素8; 内皮缩血管肽1

    近年来机械通气相关肺损伤（ventilatorinduced lung injury, VILI）越来越引起人们的重视，针对这一问题而进行的各种肺保护策略的研究已成为机械通气研究领域的热点［1-2］. 反比通气（inverse ratio ventilation, IRV）和呼气末正压通气（positive endexpiratory pressure, PEEP）是两种重要的肺保护策略，其主要机制是通过减小呼吸过程中萎陷肺泡与膨胀或正常肺泡之间的剪切力来减小肺损伤［3-4］.  我们通过比较两种肺保护策略对油酸肺损伤兔肺泡灌洗液及外周血中炎症因子的不同影响，探讨两种肺保护通气策略的优劣.

    1材料和方法

    1.1材料健康成年雄性新西兰白兔16只，体质量2.3～3.0（平均2.6）kg，均由解放军总动物中心［许可证号SCXK（京）20020005］提供，动物饲养环境，温度18～ 22℃，湿度40%～70%.

    1.2方法将动物随机分为两组,每组8只. IRV组，呼吸频率30次/min，I∶E=3∶1，潮气量12 mL/kg，PEEP=0；PEEP组，呼吸频率40次/min，I∶E=1∶2，潮气量10 mL/kg，PEEP=20 cmH2O. 两组均以容量控制通气. 吸氧浓度(FiO2)=0.5. 调整潮气量维持PCO2 40 cmH2O，MAP维持在50 mmHg(1 mmHg=0.133 kPa)以上. 在0, 30, 60, 90及120 min抽动脉血监测血气指标.

    各组动物在实验前均禁食12 h,用30 g/L戊巴比妥钠(1 mL/kg)经耳缘静脉麻醉后, 取仰卧位固定于手术台上,分别行右颈总动脉和颈外静脉插管及气管切开、气管内插管, 连接PB840呼吸机（PuritonBenett公司，美国）,静脉注射潘库溴铵0.2 mg/kg抑制自主呼吸,整个实验过程中以0.1 mg/(kg・h)的剂量持续静脉滴注维持肌松, 30 min内iv油酸(0.06 mL/kg),建立油酸ALI模型. 用Spacelabs多功能监护仪（Spacelabs Nedical公司，美国）持续监测动脉平均血压、心率.

    实验后0, 30, 60和120 min，由右颈外静脉导管采集混合静脉血各3 mL,分置于含有100 g/L EDTA的试管中,4℃ 3000 r/min离心15 min,分离血浆或血清,-20℃保存待测血浆TNFα，IL8和ET1含量. 各组动物均于实验完成后120 min时放血处死,立即开胸取肺,左肺生理盐水灌洗3次，每次10 mL,将灌洗液混合，3000 r/min离心15 min,取上清，-20℃保存待测BALF中TNFα, IL8, ET1含量. 上述用放免法检测，试剂盒均由解放军总医院放免所提供，将右肺称湿质量后置于75℃烤箱72 h取出称干质量. 肺水含量按下列公式： 肺水质量分数(g/kg)=(肺湿质量-肺干质量)/肺湿质量×100%.

    统计学处理:各组数据以x±s表示,用SPSS10.0统计软件进行数据分析,重复测量方差分析及LSDt检验.