雾化吸入氯胺酮对机械通气致肺损伤家兔TNF-α、IL-6、IL-10的影响

The influence of nebulized inhalation of ketamine on TNF-α,IL-6 and IL-10 in rabbits with ventilator-induced lung injury

目的探讨氯胺酮雾化吸入对呼吸机所致肺损伤(ventilator-induced lung injury,VILI)家兔模型的影响。方法 48只家兔,随机均分为对照组(C组)、机械通气损伤模型组(V组)、生理盐水对照组(NS组)和不同浓度氯胺酮处理组(分别为K1组、K2组和K3组)。除C组外,其他组均给予大潮气量通气(VT=40 mL/kg)4小时,K1、K2、K3、NS组在给予大潮气量通气同时间断雾化吸入容量为4ml/kg/h、浓度为12.5 mg/ml、25 mg/ml、50mg/ml的氯胺酮持续10min/h或等量生理盐水。4小时后测定肺湿/干重比、肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)变化。结果与C组比较,V组和NS组肺W/D比值和BALF中IL-6、TNF-α含量明显升高(P<0.05)。与V组比较,K3组肺W/D比值和BALF中TNF-α和IL-6含量减少的同时,IL-10含量增高,且改变有显著性差异。结论氯胺酮雾化吸入对机械通气所致兔肺损伤有保护作用,高浓度氯胺酮则保护作用更显著,该作用与氯胺酮雾化吸入减少炎性介质的释放有关。

Objective To investigate the protective effect in ventilator-induced lung injury rabbits by nebulized inhalation of Ketamine. Methods 48 adult rabbits were divided into six groups randomly （n=8）： control group（C）, lung injury induced by ventilator group（V）, normal saline group （NS） and three treatment groups of different concentration of ketamine （K1, K2, K3）. All rabbits were given large tidal volume ventilation （VT = 40ml/kg, respiratory rate 12 times/min） for 4 h excluding control group which were only preformed an operation of tracheotomy and kept spontaneous breathing. Then ketamine treatment rabbits were inhaled with either 12.5 mg/kg, 25 mg/kg or 50 mg/kg ketamine, 4 ml/kg/h by intermittence for 10 min/h. Normal saline group rabbits were inhaled nebulized saline 4ml/kg/h by intermittence for 10min/h. The levels of TNF-α, IL-6 and IL-10 in bronchoalveolar lavage fluid （BALF） and wet/dry radio were detected 4 h later. Results As compared with the C group, the wet/dry radio, concen- tration of IL-6 and TNF-a were significantly increased in V and NS groups （P〈0.05）. 50 mg/kg ketamine （K3 group） significantly decreased the west/ dri radio, concentration of TNF-α, IL-6, the levels of IL-10 significantly increased compared with the V group （P〈0.05）. Conclusion Nebulized ketamine inhalation could attenuate the lung injury induced by ventilator in rabbits, which is probably related to reducing the inflammation mediator release.