己酮可可碱在高机械通气诱导大白鼠肺损伤炎性反应中的作用

Effect of pentoxifylline on ventilator-induced lung injury in rats

目的探讨己酮可可碱(pentoxifylline,PTX)在大容量机械通气诱导的大白鼠肺损伤炎性反应中的作用。方法大白鼠在接受4h大容量机械通气时,治疗组(8只)静脉给予PTX,对照组(15只)静脉给予生理盐水,比较通气前后气道灌洗液中血栓烷B2(thromboxane B2,TXB2)、肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)、血小板活性因子(platelet activating factor,PAF)、肺组织髓过氧化物酶(myeloperoxidase,MPO)水平和肺组织湿干重量比。结果气道灌洗液中TXB2治疗组通气前为(17±4)ng/L,通气后为(13±1)ng/L,对照组通气前为(15±2)ng/L,通气后为(21±2)ng/L,两组通气后比较差异有统计学意义(P<0.01);TNF-α治疗组通气前为(39±19)ng/L,通气后为(245±76)ng/L,对照组通气前为(29±16)ng/L通气后为(620±112)ng/L,两组通气后比较差异有统计学意义(P<0.01);PAF两组通气后比较差异无统计学意义。治疗组肺组织MPO为(0.6±0.1)OD/g,对照组为(1.4±0.7)OD/g(P<0.01);治疗组肺组织湿干重量比为(6.3±0.3)g/g,对照组为(7.3±0.4)g/g(P<0.01)。结论PTX在抑制大容量机械通气诱导大白鼠肺损伤的炎性反应中有一定的积极作用。

Objective To evaluate the efficacy of pentoxifylline （PTX） in the attenuation of lung inflammation induced by large tidal volume ventilation. Methods Adult rats were anesthetized, paralyzed, tracheotomized and mechanically ventilated for a period of 4 h. Animals were randomly assigned to placebo （n=15）, or PTX group （n=8） that received PTX [100 mg/kg over 30 min, followed by a continuous infusion of 50 mg/（kg · h）] before and during exposure to the large tidal volume ventilation （20 ml/kg）. Tracheoalveolar fluid thromboxane B2 （TXB2）, tumor necrosis factor alpha （TNF-a） and platelet activating factor （PAF） were measured at baseline and after 4 h of ventilation. Lung tissue myeloperoxidase （MPO） and wet/dry lung weights were assessed upon completion Of the 4 h study. Data were analyzed using ANOVA. Results A significant decrease was observed in tracheoalveolar TXB2 from（17 ± 4） ng/L before ventilation to （13 ± 1） ng/L after 4 h ventilation in the PTX group compared to placebo from （15±2）ng/L to （21±2）ng/L（P〈0.01）. A similar change was found tracheoalveolar TNF-a levels from（39 ± 19） ng/L before ventilation to （245 ± 76） ng/L after 4 h ventilation in the PTX group compared to placebo from（29 ± 16） ng/L to（620 ± 112） ng/L（P〈 0.01）. Tracheoalveolar PAF levels were not significantly different between the two groups in animals that survived the 4 h. Lung MPO was compared between PTX and placebo [（0.6±0.1） OD/g vs（1.4 ±0.7） OD/g, P〈0.01], and Wet /dry lung weights was also compared [（6.3±0.3）g/g vs （7.3± 0.4）g/g, P〈0.01]. Conclusions PTX may be effective in reducing inflammatory lung injury associated with high tidal volume mechanical ventilation.