右美托咪定对大鼠离体肺缺血再灌注所致线粒体损伤的影响

目的：探究右美托咪定（dexmedetomidine，Dex）对大鼠离体肺缺血再灌注所致线粒体损伤的影响。方法：将SD大鼠随机分成4组（n=6）：对照组（C组）、缺血再灌注组（IR组）、1 nmol/L Dex组（D1组）、10 nmol/L Dex组（D10组），制备大鼠离体肺缺血再灌注模型。记录平衡末（T0）、再灌注即刻（T1）、再灌注30 min（T2）和再灌注60 min（T3）时的潮气量（tidal volume，VT）、肺顺应性（compliance，Cdyn）、气道阻力（airway resistance，Raw）和肺静脉氧分压（oxygen partial，PaO2）；测定肺湿/干重比；HE染色观察组织病理学改变；测定灌流末流出液乳酸脱氢酶（LDH）活性和肺组织中活性氧（ROS）、丙二醛（MDA）、三磷酸腺苷（ATP）含量以及超氧化物歧化酶（SOD）活性。分离肺组织线粒体，检测线粒体肿胀程度和线粒体膜电位（MMP）。结果：与C组相比，IR组、D1组、D10组肺功能不同程度降低，LDH活性升高，ROS、MDA增加，SOD活性下降，ATP生成减少，线粒体肿胀程度升高，MMP下降（P < 0.05）；与IR组相比，D1组、D10组肺功能改善，病理显示肺损伤明显减轻，LDH释放减少，ROS、MDA含量减少，SOD活性升高，ATP生成增加，线粒体肿胀程度减轻，MMP上升（P < 0.05）；与D1组相比，D10组改善肺功能作用更明显，Raw下降，LDH活性降低，SOD活性升高，线粒体肿胀程度减轻（P < 0.05）。结论：右美托咪定减轻了离体肺缺血再灌注损伤，其机制可能与减轻线粒体损伤，减少氧化应激反应有关。

Effect of dexmedetomidine on ischemia/reperfusion-induced mitochondrial injury in a rat ex vivo lung model

Objective: To evaluate the effect of dexmedetomidine on ischemia/reperfusion-induced mitochondrial injury in a rat ex vivo lung model. Methods: Sprague-Dawley rats were randomly divided into four groups(n=6 each): control group(group C), ischemia/reperfusion group(group IR),lnM of dexmedetomidine group(group D1) and 10nM of dexmedetomidine group (group D10). An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Airway pressure (Raw), lung compliance (Cdyn), perfusion flow (VT) and pulmonary venous oxygen partial pressure (PaO2) were recorded at four points in time: the end of balance(T0), 0 min(T1), 30 min(T2) and 60 min(T3) of reperfusion. Lung injury was assessed by histopathological changes and lung wet/dry (W/D) weight ratio. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), and adenosine triphosphate (ATP) were measured. Mitochondrial swelling and mitochondrial membrane potential (MMP) were measured. Result: Compared with group C, the pulmonary function of group IR, D1 and D10 worsened. LDH activity increased, as well as the content of ROS and MDA. SOD activity and the production of ATP decreased. The level of mitochondrial swelling increased, and mitochondrial MMP decreased in group D1 and D10 (P<0.05). Compared with group IR, the pulmonary function of group D1 and D10 was improved, and pathological changes showed that lung injury was significantly reduced. The activity of LDH decreased, content of ROS and MDA decreased, SOD activity and ATP production increased, mitochondrial swelling decreased, MMP increased (P < 0.05). Compared with D1 group, the pulmonary function of D10 group was improved, Raw and LDH activity decreased while SOD activity increased, and mitochondrial swelling reduced (P<0.05). Conclusion: Dexmedetomidine can alleviate lung ischemia/reperfusion injury in a rat ex vivo lung model, and the mechanism may be related to alleviating mitochondrial injury and oxidative stress.