CAJ | 학술논문

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.
목적 평개우미탁미정대견궤계통기상관성폐손상시NF-κB활성적영향.방법 건강비격견30지,체중10 ～ 12 kg,채용수궤수자표법분위5조(n=6):대조조(C)、궤계통기(MV조)화불동제량우미탁미정조(DEX1-3조).C조행기관삽관술자주호흡,MV조호흡궤궤계통기4h,흡입양농도50％、통기빈솔15차/min、조기량20ml/kg、PEEP 2 cm H2O.DEX13조우기관삽관전20 min내정맥수주우미탁미정0.5、1.0、2.0 μg/kg부하제량5ml,0.5、1.0、2.0μg· kg-1 ·h-1유지4h.분별우기출상태、궤계통기1、2화4h시취고동맥혈측정PaO2,궤계통기4h후처사동물취폐,칭중,계산폐조직습간중비(W/D),측정수과양화물매(MPO)활성,Western blot법측정NF-κB p65단백적표체수평.채용PCR법검측폐조직TNF-α mRNA표체.결과 여C조비교,MV조폐조직W/D、MPO활성、NF-κB p65단백화TNF-α mRNA표체수평승고(P＜0.05);여MV조비교,DEX2화DEX3조폐조직MPO활성、NF-κB p65단백화TNF-α mRNA표체수평강저,W/D차이무통계학의의(P＜0.05).결론 우미탁미정가억제NF-κB활성감경염성반응,종이개선견궤계통기상관성폐손상.
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.