右美托咪定对烫伤致大鼠急性肺损伤的影响

Effect of dexmedetomidine on scalds-induced acute lung injury in rats

目的 评价右美托咪定对烫伤致大鼠急性肺损伤的影响.方法 雄性成年SD大鼠75只,体重200 ～ 220 g,采用随机数字表法分为5组（n=15）：对照组（C组）、烫伤组（S组）、右美托咪定组（D组）、α-银环蛇毒素组（α-BGT组）、右美托咪定＋α-银环蛇毒素组（D＋α-BGT组）.S组、D组、α-BGT组和D＋α-BGT组将大鼠背部皮肤（约30％体表面积）脱毛后浸入98℃热水中12s制备烫伤模型;C组大鼠背部皮肤浸于37℃温水中12 s.造模后24 h内腹腔注射乳酸钠林格氏液进行容量复苏治疗.D组造模前15 min时腹腔注射右美托咪定40ug/kg;α-BGT组造模前15 min时腹腔注射α7型烟碱乙酰胆碱受体拮抗剂α-银环蛇毒素1μg/kg;D＋α-BGT组造模前15 min时分别腹腔注射α-银环蛇毒素1 μg/kg和右美托咪定40 μg/kg.于造模后24 h时,处死大鼠,取肺组织,观察病理学结果,计算肺含水率,测定髓过氧化物酶（MPO）活性,采用ELISA法检测IL-1β、TNF-α及IL-6的含量,采用Western blot法检测核蛋白NF-κB的表达水平.结果 与C组比较,S组、α-BGT组和D组肺组织含水率、MPO活性、IL-1β、TNF-α及IL-6的含量升高,NF-κB表达上调（P＜0.05）;与S组比较,D组和D＋α-BGT组肺组织含水率、MPO活性、IL-1β、TNF-α及IL-6的含量降低,NF-κB表达下调（P＜0.05）,α-BGT组上述指标差异无统计学意义（P＞0.05）,病理学损伤减轻;与D组比较,D＋α-BGT组肺组织含水率、MPO活性、IL-1β、TNF-α及IL-6的含量升高,NF-κB表达上调（P＜0.05）,病理学损伤加重.结论 右美托咪定可减轻烫伤致大鼠急性肺损伤.

Objective To evaluate the effect of dexmedetomidine on acute lung injury induced by scalds in rats.Methods Seventy-five male Sprague-Dawley rats,weighing 200-220 g,were randomly divided into 5 groups （n =15 each） using a random number table：control group （group C）,scald group （group S）,dexmedetomidine group （group D）,α-bungarotoxin （α-BGT） group,and dexmedetomidine＋ α-BGT group （group D＋α-BGT）.About 30% of the total body surface was shaved and then exposed to 98 ℃ water for 12 s in S,D,α-BGT and D＋α-BGT groups.The back of rats was exposed to 37 ℃ water for 12 s in group C.Rats were resuscitated with lactated Ringer＆#39;s solution injected intraperitoneally according to Parkland formula within 24 h after establishment of the model.In D,α-BGT,and D＋α-BGT groups,dexrnedetomidine 40 μg/kg,α7 nicotinic acetylcholine receptor antagonist α-BGT 1 μg/kg,and α-BGT 1 μg/kg plus dexmedetomidine 40 μg/kg were injected intraperitoneally,respectively,at 15 min before establishnent of the model.At 24 h after establishment of the model,the rats were sacrificed,and lungs were removed for examination of the pathological changes and for determination of myeloperoxidase （MPO） activity,in terleukin-1beta （IL-1β）,tumor necrosis factor-alpha （TNF-α）,and IL-6 contents （by enzyme-linked immunosorbent assay）,and nucleoprotein factor kappa B （NF-κB） （by Western blot）.The lung water content [（wet weight-dry weight）÷wet weight×100%] was calculated.Results Compared with group C,the lung water content,MPO activities,and contents of IL-1β,TNF-α and IL-6 were significantly increased,and the expression of NF-κB was up-regulated in S,α-BGT and D groups （P〈0.05）.Compared with group S,the lung water content,MPO activities,and contents of IL-1β,TNF-α and IL-6 were significantly decreased,and the expression of NF-κB was down-regulated in D and D＋α-BGT groups （P〈0.05）,and no significant change was found in the parameters mentioned above （P〉0.05）,and the pathological changes were significantly attenuated in group α-BGT.Compared with group D,the lung water content,MPO activities,and contents of IL-1β,TNF-α and IL-6 were significantly increased,the expression of NF-κB was up-regulated （P〈0.05）,and the pathological changes were aggravated in group D ＋ α-BGT.Conclusion Dexmedetomidine can mitigate scalds-induced acute lung injury in rats.