右美托咪定对大鼠肺缺血再灌注时炎症反应及脂质过氧化反应的影响：离体实验

Effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia-reperfusion in rats： an in vitro experiment

目的探讨右美托咪定对大鼠肺缺血再灌注损伤时炎症反应及氧化应激的影响。 方法SPF级雄性成年SD大鼠，体重250～320 g，制备离体肺灌注模型30个，采用随机数字表法分为3组（n ＝ 10）：假手术组（S组）、肺缺血再灌注组（I/R组）和右美托咪定组（D组）。S组持续灌流150 min；I/R组灌流15 min后，停止通气和灌流60 min，然后继续通气和灌流75 min，制备大鼠肺缺血再灌注损伤模型；D组用含10 nmol/L右美托咪定的K-H液灌流15 min后，停止通气和灌流60 min，然后继续通气和灌流含10 nmol/L右美托咪定的K-H液75 min。分别于灌流10 min、恢复灌流15、45和75 min时，记录肺气道阻力、肺顺应性、灌注流量和肺动脉氧分压（PaO2）；于恢复灌流75 min时取肺组织，测定湿重/干重（W/D）比值，观察肺组织病理学结果和超微结构。分别采用改良邻苯三酚法和硫代巴比妥酸法分别测定SOD活性和MDA含量；采用Western blot法测定肺组织β-内啡肽及IL-8的表达水平。 结果与S组比较，I/R组、D组恢复灌流期间气道阻力升高，肺顺应性、灌注流量和PaO2均降低，肺组织W/D比值和MDA含量升高，SOD活性降低，β-内啡肽和IL-8表达上调（P〈0.05）；与I/R组比较，D组恢复灌流期间气道阻力降低，肺顺应性、灌注流量和PaO2均升高，肺组织W/D比值和MDA含量降低，SOD活性升高，β-内啡肽和IL-8表达下调（P〈0.05），肺组织病理学损伤减轻。 结论右美托咪定减轻大鼠肺缺血再灌注损伤的机制可能与抑制肺组织脂质过氧化反应及炎症反应有关。

Objective To investigate the effects of dexmedetomidine on inflammatory response and lipid peroxidation during lung ischemia-reperfusion （I/R） in rats. Methods Thirty lungs, which were i- solated from SPF adult male Sprageue-Dawley rats, in which the model of isolated lung perfusion was suc- cessfully established, were divided into 3 groups （n = 10 each） using a random number table： sham oper- ation group （ S group）, I/R group and dexmedetomidine group （ D group）. The lungs were subjected to 60 rain of ischemia and apnea after 15-rain ischemia followed by 75 min of reperfusion and ventilation to estab- lish the model of isolated lung I/R injury. In group D, the lungs were perfused with K-H solution containing 10 nmol/L dexmedetomidine for 15 rain and then subjected to 60 rain of ischemia and apnea followed by ven- tilation and reperfusion with K-H sloution containing 10 nmol/L dexmedetomidine for 75 rain. Airway resist- ance, lung compliance, perfusion flow and partial pressure of arterial oxygen （PaO2 ） were recorded at 10 min of perfusion （T0） and 15, 45 and 75 min after restoration of perfusion （Tl-3）. Lung tissues were ob- tained at 75 rain after restoration of perfusion for determination of wet/dry weight ratio （W/D ratio） and for examination of pathological changes and uhrastructure of lungs. The activity of superoxide dismutase （SOD） and content of malondialdehyde （MDA） in lung tissues were measured by improved pyrogallol au-toxidation method and thiobarbituric acid method, respectively. The expression of 13-endorphin and interleu- kin-8 （IL-8） in lung tissues was detected by Western blot. Results Compared with group S, the airway resistance was significantly increased, and the lung compliance, perfusion flow and PaO2 were decreased during the perfusion restoration period, the W/D ratio and content of MDA were increased, the activity of SOD was decreased, and the expression of 13-endorphin and IL-8 was up-regulated in I/R and D groups （P〈0. 05）. Compared with group I/R, the airway resistance was significantly decreased, and the lung compliance, perfusion flow and PaO2 were increased during the peffusion restoration period, the W/D ratio and content of MDA were decreased, the activity of SOD was increased, the expression of 13-cndorphin and IL-8 was down-regnlated （P〈0. 05） , and the pathological changes of lungs were significantly attenuated in group D. Conclusion The mechanism by which dexmcdetomidine reduces lung I/R injury may be related to inhibiting lipid peroxidation and inflammatory response of lung tissues in rats.