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目的探讨氯胺酮雾化吸入对机械通气所致肺损伤兔模型的保护作用及其机制。方法 48只家兔,随机分为正常对照组(C组)、模型组(V组)、生理盐水组(NS组)和氯胺酮组(分别为K1组、K2组和K3组),每组8只。除C组外,其他组均给予大潮气量(40 mL·kg~(-1))通气4 h,K1组、K2组、K3组、NS组在给予大潮气量通气同时间断雾化吸入氯胺酮(33.3、66.6、133.2 mg·kg~(-1))或等量生理盐水,每小时持续10 min。实验中连续监测平均动脉血压(MAP)、心率(HR)、气道峰压(P_(peak))和平台压(P_(plat)),每间隔1 h测定动脉氧分压(PaO_2),计算PaO_2/FiO_2。测定肺组织湿干重比,肺组织中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性和肿瘤坏死因子α(TNF-α)水平,以及支气管肺泡灌洗液(BALF)中蛋白含量和细胞数。结果 C组在实验过程中MAP、HR、P_(peak)、P_(plat)均较为平稳,PaO_2/FiO_2无明显变化。其他五组MAP、HR、PaO_2/FiO_2呈不同程度下降,P_(peak)、P_(plat)呈上升趋势,其中V组和NS组变化明显,K3组P_(peak)和P_(plat)低于同时点V组、NS组,通气4 h时PaO_2/FiO_2高于V组、NS组、K1组和K2组,差异均有显著意义(P<0.05)。与C组比较,V组和NS组BALF中蛋白含量、细胞总数及肺组织湿干重比、TNF-α水平、MPO活性增高,SOD活性降低(P<0.05)。与V组、NS组比较,K3组BALF中蛋白含量、细胞总数及肺组织湿干重比、TNF-α水平、MPO活性降低,SOD活性增高(P<0.05)。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,高浓度氯胺酮作用明显,可能与氯胺酮雾化吸入减少炎性介质的释放、改善氧化应激反应有关。
Objective To investigate the protective effect of ketamine inhalation on lung injury induced by mechanical ventilation in rabbits and its mechanism. Methods 48 rabbits were randomly divided into normal control group (C group), model group (V group), normal saline group (NS group) and ketamine group (K1 group, K2 group and K3 group) only. In addition to group C, the other groups were given high tidal volume (40 mL · kg -1) ventilation for 4 hours. K1, K2, K3 and NS groups were given high tidal volume ventilation while intermittent inhalation of ketamine (33.3 , 66.6, 133.2 mg · kg -1) or the same amount of normal saline for 10 min every hour. The mean arterial blood pressure (MAP), heart rate (HR), peak airway pressure (P_ (peak)) and plateau pressure (P plat) were continuously monitored in the experiment. The arterial oxygen pressure (PaO_2) PaO_2 / FiO_2. The wet / dry ratio of lung tissue, the level of MPO, SOD and the level of tumor necrosis factor α (TNF-α) in lung tissue were measured, and bronchoalveolar lavage fluid (BALF) Protein content and cell number. Results The MAP, HR, P_ (peak) and P_ (plat) in group C were stable and PaO_2 / FiO_2 did not change significantly during the experiment. The levels of MAP, HR and PaO 2 / FiO 2 in the other five groups decreased to different extents, while P peak and P plat increased. The changes of V group and NS group were obvious. The P peak and P plat of K 3 group were lower than At the same time point V, NS group, PaO 2 / FiO 2 higher than V group, NS group, K 1 group and K2 group 4 h after ventilation, the difference was significant (P <0.05). Compared with group C, the protein content, the total number of cells, the ratio of wet to dry weight, the level of TNF-α, the activity of MPO and the activity of SOD of BALF in group V and group NS were decreased (P <0.05). Compared with V group and NS group, the content of protein, the total number of cells, the ratio of wet to dry weight of lung tissue, the level of TNF-α, the activity of MPO and the activity of SOD in K3 group increased (P <0.05). Conclusion Ketamine inhalation has protective effect on lung injury induced by mechanical ventilation in rabbits. High concentrations of ketamine have obvious effects, which may be related to the inhalation of ketamine to reduce the release of inflammatory mediators and the improvement of oxidative stress response.