氯胺酮雾化吸入减轻机械通气所致家兔肺损伤  

Attenuating ventilator-induced lung injury in rabbits by nebulized inhalation of ketamine

作　　者：丰浩荣[1] 葛伟[2] 王祥和[1] 许鹏程[2] 

机构地区：[1]中国人民解放军98医院麻醉科,浙江湖州313000 [2]徐州医学院江苏省麻醉学重点实验室,江苏徐州221006

出　　处：《中国新药与临床杂志》2013年第11期891-896,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：南京军区科技创新课题项目(09MA009);浙江省湖州市科技局自然科学基金项目(2009YSB20)

摘　　要：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。AIM To investigate the protective effects in ventilator- induced lung injury rabbits by nebulized inhalation of ketamine. METHODS Forty- eight rabbits were divided into six groups randomly as following （n = 8） ： normal control group （C） , lung injury model 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 （40 mL·kg-1） for 4 h excluding group C. The rabbits in group K1, K2, K3 and NS were inhaled with ketamine 33.3, 66.6, 133.2 mg·kg-1 and NS for 10 min per hour. The mean arterial blood pressure （MAP）, heart rate （HR）, peak airway pressure （Ppeak） and plateau pressure （Pplat） changes were continuous monitored, and the PaO2/FiO2 value was calculated by measuring the arterial oxygen （PaO2） at intervals of 1 h. The lung tissue was collected 4 h later for detecting the activities of myeloperoxidase （MPO） and superoxide dismutase （SOD）, the TNF-α content and wet to dry ratio （W/D） of lung. The concentration of protein, the sum of total cells and the proportion of neutrophile in bronchoalveolar lavage fluid （BALF） were observed. RESULTS The MAP, HR, Ppeak, Plat and PaO2/FiO2 of group C were relatively stable during the experiment, while MAP, HR and PaO2/TiO2 decreased and Ppeak, Pplat increased in group V, NS and K, especially in group V and NS. The levels of Ppeak and Pplat in the group K3 were lower than those in the group V and NS at the same time point （P 〈 0.05）. Compared with group V, NS, K1 and K2, the PaO2/FiO2 in the group K3 increased 4 h after ventilated （P 〈 0.05）. Compared with the group C, the protein and the sum of total cells in BALF, the W/D of lung, the TNF-α content and activity of MPO were significantly increased in the group V and NS （P 〈 0.05）, while activity of SOD decreased （P 〈 0.05）. Compared with the group V and NS, the protein and the sum of total cells in BALF,

关 键 词：氯胺酮 投药 吸入 呼吸 人工 呼吸机相关性肺损伤 

分 类 号：R-332[医药卫生]