右美托咪啶对肺缺血/再灌注诱发小鼠肾脏超微结构改变的影响

Effect of dexmedetomidine on renal injury induced by lung ischemia/reperfusion in mice

目的:评价右美托咪啶对小鼠肺缺血/再灌注诱发肾脏损伤的影响。方法:雄性健康SPF级C57BL/6J小鼠50只,体重20 g^24 g,8~10周龄,采用随机数字表法,将其分为5组(n=10):假手术组(sham组)、肺缺血/再灌注损伤组(I/R组)、肺缺血/再灌注+生理盐水组(NS组)、右美托咪啶组(Dex组)、右美托咪啶+阿替美唑(Atip)(DA组)。采用小鼠在体左侧肺门夹闭30 min再灌注180 min方法制备肺缺血/再灌注损伤(I/R)模型。Dex组在肺门阻断前30 min腹腔注射右美托咪啶20μg/kg,NS组为用同Dex组等体积的生理盐水替代Dex,DA组腹腔注射右美托咪啶(20μg/kg)+阿替美唑(250μg/kg),其余处理同I/R组。再灌注结束后静脉取血ELISA法检测血浆中IL-1β和TNF-α浓度;取双肾组织,透射电镜下观察肾组织病理学结果。结果:与对照组相比,其余组血浆IL-1β和TNF-α浓度明显升高,肾组织病理学损伤明显加重;与I/R、NS、DA组相比,Dex组IL-1β和TNF-α浓度明显下降,差异有统计学意义(P<0.05),且肾组织超微结构损伤有所减轻。结论:右美托咪啶预先给药可减轻小鼠肺缺血/再灌注诱发肾脏损伤,其机制可能与抑制炎性反应有关。

Objective： To evaluate the effect of dexmedetomidine（ Dex） on renal injury induced by lung ischemia/reperfusion（ I/R） in mice. Methods： Fifty healthy SPF male C57 BL/6 J mice,weighing 20 g - 24 g,aged 8 - 10 weeks,were randomly divided into five groups（ n = 10 each） ： sham operation group（ sham group）,lung ischemia/reperfusion group（ I/R group）,lung ischemia/reperfusion and normal saline group（ NS group）,dexmedetomidine group（ Dex group）,dexmedetomidine and atipamezole group（ DA group）. Lung ischemia/reperfusion model was established by occlusion of the left pulmonary artery for 30 min followed by 180 min reperfusion in mice. In Dex and DA groups,dexmedetomidine 20 μg/kg and dexmedetomidine 20 μg/kg plus atipamezole 250 μg/kg were injected intraperitoneally respectively at 30 min before establishment of the model,isopyknic normal saline instead of Dex were injected intraperitoneally in NS group. After the experiment the mice were killed and plasma IL-1 beta and tumor necrosis factor α（ TNF-α） concentration were detected by ELISA; the renal tissues were harvested to observe ultra structure under electron microscope. Results： Compared with sham group,the concentrations of IL-1β and TNF-α in other groups were increased significantly and the structure damages of renal tissues observed under electron microscope in other groups were more serious than those of sham group. Compared with I/R group,NS groups and DA group,the concentrations of IL-1β and TNF-α in Dex group were significantly lower（ P0.05） and the structure damages of renal tissues observed under electron microscope in Dex group were slighter. Conclusion： Dexmedetomidine pretreatment can attenuate renal injury induced by lung ischemia/reperfusion and the mechanism may be related to inhibition of inflammatory responses.