右美托咪定对犬机械通气相关性肺损伤时NF-κB活性的影响  

Effect of dexmedetomidine on NF-κB activity during ventilator-induced lung injury in dogs

作　　者：陈畅[1] 张宗泽[1] 陈凯[1] 郭伟[1] 彭勉[1] 王焱林[1] 

机构地区：[1]武汉大学附属中南医院麻醉科,430071

出　　处：《中华麻醉学杂志》2013年第10期1239-1241,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81000318）;武汉青年科技晨光计划项目（201271031425）;湖北省卫生厅基金（JX5B16）

摘　　要：目的 评价右美托咪定对犬机械通气相关性肺损伤时NF-κB活性的影响.方法 健康比格犬30只,体重10 ～ 12 kg,采用随机数字表法分为5组（n=6）：对照组（C）、机械通气（MV组）和不同剂量右美托咪定组（DEX1-3组）.C组行气管插管术自主呼吸,MV组呼吸机机械通气4h,吸入氧浓度50％、通气频率15次/min、潮气量20ml/kg、PEEP 2 cm H2O.DEX13组于气管插管前20 min内静脉输注右美托咪定0.5、1.0、2.0 μg/kg负荷剂量5ml,0.5、1.0、2.0μg· kg-1 ·h-1维持4h.分别于基础状态、机械通气1、2和4h时取股动脉血测定PaO2,机械通气4h后处死动物取肺,称重,计算肺组织湿干重比（W/D）,测定髓过氧化物酶（MPO）活性,Western blot法测定NF-κB p65蛋白的表达水平.采用PCR法检测肺组织TNF-α mRNA表达.结果 与C组比较,MV组肺组织W/D、MPO活性、NF-κB p65蛋白和TNF-α mRNA表达水平升高（P＜0.05）;与MV组比较,DEX2和DEX3组肺组织MPO活性、NF-κB p65蛋白和TNF-α mRNA表达水平降低,W/D差异无统计学意义（P＜0.05）.结论 右美托咪定可抑制NF-κB活性减轻炎性反应,从而改善犬机械通气相关性肺损伤.Objective To evaluate the effect of dexmedetomidine on NF-κB activity in ventilator-induced lung injury in dogs.Methods Thirty healthy 5-year-old Beagles,weighing 10-12 kg,were randomly assigned into 5 groups （n =6 each） using a random number table：control group （group C）,mechanical ventilation （MV） group and 3 different concentrations of dexmedetomidine groups （groups DEX1-3）.The animals were anesthetized with pentobarbital sodium,ketamine and atropine.The rats were tracheostomized and spontaneous breathing was maintained in group C,while the rats were tracheostomized and mechanically ventilated for 4 h in MV and DEX1-3 groups.Tracheal intubation was performed in all the groups.The concentration of O2 inhaled was set at 50％,respiratory rate at 15 bpm,tidal volume at 20 ml/kg,and positive end-expiratory pressure at 2 cm H2 O.A loading dose of dexmedetomidine 0.5,1.0 and 2.0 μg/kg was infused over 20 min before intubation,followed by continuous infusion （lasting for4 h） at a rate of 0.5,1.0 and 2.0μg·kg-1 ·h-1 in DEX1-3 groups,respectively.Blood samples were taken from the femoral artery at baseline state,and 1,2 and 4 h of MV for detection of PaO2.The animals were sacrificed after 4 h of MV.The lungs were removed for determination of W/D lung weight ratio （W/ D ratio）,myeloperoxidase （MPO） activity,NF-κB p65 expression （by Western blot） and TNF-α mRNA expression （by RT-PCR） in lung tissues.Results Compared with group C,W/D ratio,MPO activity,and expression of NFκB p65 and TNF-α mRNA were significantly increased in group MV （P ＜ 0.05）.Compared with group MV,MPO activity,and expression of NF-κB p65 and TNF-α mRNA were significantly decreased,and no significant change was found in W/D ratio in DEX2 and DEX3 groups （P ＜ 0.05）.Conclusion Dexmedetomidine can inhibit NF-κB activity and reduce inflammatory responses,thus improving ventilator-induced lung injury in dogs.

关 键 词：右美托咪啶 呼吸 人工 呼吸窘迫综合征 成人 炎症 

分 类 号：R614[医药卫生—麻醉学]