高频振荡通气对重度急性呼吸窘迫综合征犬肺组织炎性反应的影响

Effect of high-frequency oscillatory ventilation on inflammatory responses in lung tissues of dogs with severe acute respiratory distress syndrome

目的探讨高频振荡通气（HFOV）对重度急性呼吸窘迫综合征（ARDS）犬肺组织炎性反应的影响。方法普通级健康杂种犬，雌雄不拘，体重13．7～16．2kg，采用静脉输注油酸0．2ml／kg与等量自体血混合液的方法制备重度ARDS模型。取模型成功的犬24只，采用随机数字表法分为4组（n=6）：小潮气量常规机械通气组（CMV组）、HFOV-9Hz组、HFOV-12Hz组和HFOV-15Hz组。HFOV-9Hz组、HFOV-12Hz组和HFOV-15Hz组振荡频率分别为9、12和15Hz，其余参数为平均气道压20cmH2O，振荡压70cmH2O，FiO2 1．0；CMV组采用容量控制通气模式，PEEP5cmH2O，VT 6ml／kg，RR30次／min，吸呼比1：2，FiO2 1．0。机械通气4h时处死动物，取肺组织，计算湿重，干重（W／D）比值；采用ELISA法测定TNF-α、IL-6和IL-10含量；采用Western blot法测定血管内皮钙黏蛋白（VE-Cadherin）的表达水平；光镜下观察肺组织病理学结果，并进行肺损伤评分。结果与CMV组。比较，其余3组肺损伤评分、肺组织W／D比值、TNF—α及IL-6含量降低，IL-10升高，VE-Cadherin表达上调（P〈0．05）；与HFOV-9Hz组比较，HFOV-15Hz组肺损伤评分、肺组织W／D比值、TNF-α及IL-6含量降低，IL-10升高，VE-Cadherin表达上调，HFOV-12Hz组肺组织IL-6含量降低（P〈0．05）。结论相对于小潮气量机械通气，HFOV可明显抑制重度ARDS犬急性肺组织炎性反应，该作用可能参与了其肺保护性通气效应的机制。

Objective To investigate the effect of high-frequency oscillatory ventilation （HFOV） on inflammatory responses in lung tissues of dogs with severe acute respiratory distress syndrome （ARDS）. Methods Heahhy mongrel dogs of both sexes, weighing 13.7-16.2 kg, in which severe ARDS was induced by intravenous infusion of the mixture of oleic acid 0.2 ml/kg and autologous blood （ equal to the volume of oleic acid）. Twenty-four dogs with severe ARDS were randomly divided into 4 groups （n= 6 each） using a random number table： conventional mechanical ventilation with low tidal volume group （group CMV） , HFOV-9 Hz group, HFOV-12 Hz group and HFOV-15 Hz group. In HFOV-9 Hz, HFOV-12 Hz and HFOV-15 Hz groups, the frequency was 9, 12, and 15 Hz, respectively, mean airway pressure 20 cm H2O, oscillation pressure 70 cmHH2O, and inspired oxygen fraction ratio 1.0. In group CMV, the animals were mechanically ventilated in volume-controlled mode, with positive end-expiratory pressure 5 cmH20, tidal volume 6 ml/kg, respiratory rate 30 breaths/min, inspiratory/expiratory ratio 1 ： 2, and inspired oxygen fraction ratio 1.0. At 4 h of ventilation, the animals were sacrificed, and lungs were removed for determination of wet/dry weight （W/D） ratio, contents of tumor necrosis factor-alpha （TNF- α） , interleukin-6 （IL-6） and IL-10 （by enzyme-linked immunosorbent assay） , and expression of vascular endothelial （ VE）-Cadherin （by Western blot） and for microscopic examination. Lung injury scores were assessed. Results Compared with group CMV, the lung injury scores, W/D ratio, and contents of TNF-α and IL-6 were significantly decreased, the content of IL-10 was significantly increased, and the ex- pression of VE-Cadherin was significantly up-regulated in the other three groups （P〈O.05）. Compared with group HFOV-9Hz, the lung injury scores, W/D ratio and contents of TNF-α and IL-6 were significantly decreased, the content of IL-10 was significantly increased, and the expression of VE-Cadherin was significantly up-regulated in group HFOV-15 Hz, and the content of IL-6 was significantly decreased in group HFOV-12 Hz （P〈0.05）. Conclusion HFOV can significantly inhibit inflammatory responses in lung tissues of dogs with severe ARDS as compared with mechanical ventilation with low tidal volume, which may be involved in the mechanism of lung-protective ventilation effect.