α2肾上腺素能受体在右美托咪定抑制大鼠肺缺血再灌注损伤时脂质过氧化反应中的作用

Role adrenergic receptors in dexmedetomidine-induced inhibition of lipid peroxidation during lung ischemia-reperfusion injury in rats

【摘要】目的评价α2肾上腺素能受体在右美托咪定抑制大鼠肺缺血再灌注损伤时脂质过氧化反应中的作用。方法取制备成功的大鼠离体肺灌注模型32个，采用随机数字表法，将其分为4组（n=8）：对照组（C组）、缺血再灌注组（I／R组）、右美托咪定组（D组）和右美托咪定＋育亨宾组（DY组）。采用离体肺停止通气和灌流60min后恢复75min的方法制备大鼠离体肺缺血再灌注损伤模型。于复灌开始时，D组灌流液中加入2．3ng／ml右美托咪定，DY组加入2．3ng／ml右美托咪定和0．4μg／mld：肾上腺素能受体阻断剂育亨宾。于再灌注结束后即刻，取肺组织，测定肺组织湿重／干重（W／D）比值；采用HE染色法观察肺组织病理学结果；采用改良邻苯三酚法测定SOD活性，硫代巴比妥酸法测定MDA含量。结果与C组比较，I／R组、D组和DY组W／D比值和MDA含量升高，S01）活性降低（P〈0．05）；与I／R组比较，D组W／D比值和MDA含量降低，SOD活性升高（P〈O．05）；与DY组比较，D组W／D比值和MDA含量降低，SOD活性升高（P〈0．05）。D组肺组织病理学损伤较I／R组和DY组减轻。结论右美托咪定抑制大鼠肺缺血再灌注损伤时脂质过氧化反应的机制与激动α2肾上腺素能受体有关。

Objective To evaluate the role of α2 adrenergic receptors in dexmedetomidine-induced inhibition of lipid peroxidation during lung ischemia-reperfusion （I/R） injury in rats. Methods Thirty-two isolated rat lungs in which the model of isolated lung perfusion was successfully established, were divided into 4 groups （n = 8 each） using a random number table： control group （ C group） , I/R group, dexme- detomidine group （D group） and dexmedetomidine plus yohimbine group （DY group）. The isolated lungs were subjected to 60 min of ischemia and apnea followed by 75 min of reperfusion and ventilation to establish the model of isolated lung I/R injury. From the beginning of reperfusion, 2.3 ng/ml dexmedetomidine was added to the perfusion fluid in D group, and 2. 3 ng/ml dexmedetomidine and 0.4 μg/ml yohimbine （ an α2 adrenergic receptor blocker） were added to the perfusion fluid in DY group. Lung specimens were obtained immediately after the end of reperfusion for determination of the wet/dry weight ratio （W/D ratio） , superox- ide dismutase （SOD） activity （by using modified pyrogallol autoxidation method） and malondialdehyde （MDA） content （by thiobarbituric acid method） and for examination of the pathological changes （using haematoxylin and eosin staining）. Results Compared with C group, the W/D ratio and MDA content were significantly increased, and the SOD activity was deereased in I/R, D and DY groups （P〈0.05）. Com- pared with I/R group, the W/D ratio and MDA eontent were significantly decreased, and the SOD activiiy was increased in 1） group （P〈0.05）. Compared with DY group, the W/D ratio and MDA content were sig- nificantly decreased, and the SOD activity was increased in group D （P〈0.05）. The pathologieal changes of lung tissues were significantly attenuated in D group as compared with I/R and DY groups. Conclusion The mechanism by which dexmedetomidine inhibits lipid peroxidation is related to activating α2 adrenergie receptors during lung 1/R injury in rats.