不同剂量盐酸右美托咪定对犬机械通气相关性肺损伤模型中炎性因子表达的影响

Effects of Different Doses of Dexmedetomidine Hydrochloride on the Expression of Inflammatory Factors in Mechanical Ventilation-associated Lung Injury in Dogs

目的建立犬机械通气相关性肺损伤模型,评价不同剂量盐酸右美托咪定对犬机械通气相关性肺损伤炎性因子表达的影响。方法健康比格犬30只,体重10-12kg,采用随机数字表法,将其随机分为5组（n=6）：正常对照组（C）,机械通气（MV）组和不同剂量盐酸右美托咪定组（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 2cmH2O。Dex1-3组在行机械通气前20min内静脉泵入右美托咪定0.5、1.0、2.0μg/kg负荷剂量5mL,继以0.5、1.0、2.0μg/（kg·h）泵入维持4h。分别于基础状态、MV1h、MV2h、MV4h取颈静脉血,测定血清中NO水平,取颈动脉血测定PaO2。机械通气4h后颈动脉放血处死动物,测定肺组织湿重/干重比（W/D）,髓过氧化物酶（MPO）活性,RT-PCR检测肺组织NF-κB mRNA、TNF-αmRNA、iNOS mRNA表达。结果与基础值相比,MV2h、MV4h的PaO2显著降低（均P〈0.05）;与C组比较,其他各组肺组织W/D显著性增高（均P〈0.05）,MPO活性显著性增高（均P〈0.05）;与MV组比较,DEX2、3两组MPO活性显著性降低（均P〈0.05）。与基础值相比,机械通气导致血清NO水平显著增高（P〈0.05）;与MV组比较,Dex2和Dex3组在机械通气2h及4h血清NO水平显著降低（均P〈0.05）。与C组比较,MV组肺组织NF-κB mRNA、TNF-αmRNA和iNOS mRNA表达增加（均P〈0.05）;与MV组比较,Dex各组肺组织NF-κB mRNA、TNF-αmRNA和iNOS mRNA表达均降低（均P〈0.05）。结论盐酸右美托咪定可降低犬机械通气相关性肺损伤炎性因子的表达。

Objective To establish ventilator-induced lung injury models in dogs and to evaluate the effects of different doses of dexmedetomidine hydrochloride on the expression of inflammatory factors in dogs with ventilator-induced lung injury.Methods Thirty healthy Beagles weighing 10 to 12kg were randomized into 5different groups（n=6each）：control group（group C）,mechanical ventilation group（group MV）and 3dexmedetomidine groups（groups Dex1-3）.All dogs underwent endotracheal intubation.Those in group C maintained autonomous breathing.Animals in group MV and group Dex1-3were mechanically ventilated with tidal volume at 20mL/kg.The ventilation frequency was set at 15 times/min.The MV lasted for 4h with a PEEP equaling to 2cm H2O and FIO2 kept at 0.5.Dexmedetomidine was given as a loading dose of 0.5,1.0 and 2.0μg/kg over 20 min,followed by a continuous infusion of 0.5,1.0and 2.0μg/（kg·h）intravenously in group Dex.Blood samples were taken from the internal jugular vein before and 1,2 and 4h after MV for the determination of serum NO,and arterial blood samples were obtained for blood gas analysis.The animals were sacrificed after 4h MV.The lung tissues were evaluated for W/D lung weight ratio,and myeloperoxidase MPO levels.The expression of NF-κB,TNF-αand iNOS mRNA was detected by RTPCR.Results PaO2 was significantly decreased 2 and 4hafter MV as compared with that before MV（P〈0.05）.The W/D lung weight ratio and the MPO activity were significantly increased in group MV and groups Dex1,Dex2,Dex3 as compared with those in group C（P〈0.05）.The MPO activity was much lower in groups Dex2,3than in group MV（P〈0.05）.MV could lead to a significant increase in serum NO levels（P〈0.05）.The serum NO levels were profoundly decreased in groups Dex2,Dex3after 2hor 4h MV when compared with those in group MV（P〈0.05）.The mRNA expression levels of NF-κB,TNF-αand iNOS were up-regulated markedly in group MV as compared with those in group C（P〈0.05）,which could be conspicuously reversed in groups Dex1,Dex2,Dex3（P〈0.05）.Conclusion Dexmedetomidine can decrease the expression of inflammatory factors in dogs with ventilator-associated lung injury.