右美托咪定对撞击性肺损伤大鼠的肺保护作用

摘要

Objective To observe the effect of dexmedetomidine on the invasive blood pressure,blood gas analysis,NF-κB,TNF-α,IL-1β and the percentage of neutrophil in leucocyte in bronchoalveolar lavage fluid (BALF)in rats of lung injury following blunt chest trauma,and to ex-plore its mechanism.Methods Forty adult male SD rats were randomly divided into 5 groups:normal group (group C),normal plus dexmedetomidine group (group D),trauma group (group T), trauma plus dexmedetomidine group (group TD),trauma plus dexmedetomidine plus yohimbine group (group TDY).Groups C and D only inhale sevoflurane.The invasive blood pressure of rats were monitored continuely.Arterial blood gas analysis was finished before the rats died.The expres-sion of NF-κBp65 of lung tissue was detected by immunohistochemistry technology.The expression of TNF-αand IL-1βin plasma were examined by ELISA.Lung wet/dry (W/D)weight,the percentage of neutrophil in leucocyte in bronchoalveolar lavage fluid(BALF)was detected.HE staining was per-formed to observe the injury of lung tissue.Results After blunt chest trauma,The serum concentra-tion of TNF-αand IL-1β,NF-κBp65 of lung tissue,PMN and lung wet/dry (W/D)weight were signif-icantly higher in traumatic group (P < 0.05 or P < 0.01 ).The structure of alveolar was seriously damaged in sixth hour after injured.Dexmedetomidine (5 μg · kg-1 · h-1 )continuous infusion markedly decreased the lung injury because of blunt chest trauma,but this effect of dexmedetomidine could be mediated by yohimbine,at least partically.Conclusion Dexmedetomidine has a certain pro-tective effect on traumatic acute lung injury by reducing the expression of inflammatory factor in lung tissue and serum in rats.%目的：探讨右美托咪定对撞击性肺损伤大鼠肺部的保护机制。方法清洁级成年雄性 SD 大鼠40只,随机均分为五组：正常对照组(C 组)、右美托咪定组(D 组)、胸部创伤模型组(T组)、胸部创伤模型+右美托咪定处理组(TD 组)和胸部创伤模型+右美托咪定+育亨宾(α2肾上腺素能受体阻断剂)组(TDY 组)。C 和 D 组只麻醉不创伤,T、TD、TDY 组复制大鼠胸部撞击模型。持续监测五组大鼠创伤后0.5、1、2、4和6 h 的有创平均动脉血压(MIAP),处死前抽取动脉血0.5 ml 行动脉血气分析；采用免疫组织法检测肺组织 NF-κBp65的表达；酶联免疫吸附实验(ELISA)检测血清中 TNF-α和 IL-1β浓度；检测支气管肺泡灌洗液(BALF)中中性粒细胞占白细胞百分比(PMN),计算肺湿/干比(W/D)；HE 染色光镜下观察肺组织病理改变。结果创伤后0.5、1、2 h 时D 组 MIAP 明显高于 T 组,创伤后4和6 h 时 D 组 MIAP 明显低于 C 和 T 组(P <0.05)；创伤后1 h TDY 组 MIAP 明显高于,创伤后4和6 h TDY 组 MIAP 明显低于 C 和 TD 组(P <0.05)。T、TD 和TDY 组 PaO 2、PaCO 2明显低于,pH、TNF-α和 IL-1β浓度明显高于 C 组(P <0.01)。D、TD 和 TDY组 PaO 2、PaCO 2明显高于,血清 TNF-α和 IL-1β浓度明显低于 T 组(P <0.01),T 组 pH 明显高于 D组,但明显低于 TD、TDY 组(P <0.01)。D 组肺组织 NF-κBp65,T、TD 和 TDY 组肺组织 NF-κBp65、W/D 和 PMN 明显高于 C 组(P <0.05)；D、TD、TDY 组肺组织 NF-κBp65、M/D 和 PMN 明显低于 T 组(P <0.01)；TDY 组肺组织 NF-κBp65、M/D 和 PMN 明显高于 TD 组(P <0.01)。结论盐酸右美托咪定可通过抑制肺组织和血清中炎症因子的表达减轻创伤性肺损伤的程度。