右美托咪定预处理对小鼠肠缺血再灌注损伤的作用研究  

Effect of Dexmedetomidine Pretreatment on Intestinal Ischemia-reperfusion Injury in Mice

作　　者：赵京禹[1] 费翔[1] 郭徽[1] 岳琦[1] 邓城旗[1] 郝建华[1] 

机构地区：[1]解放军总医院第一附属医院麻醉科,北京100037

出　　处：《现代生物医学进展》2014年第35期6823-6826,共4页Progress in Modern Biomedicine

摘　　要：目的:右美托咪定(Dexmedetomidine,Dex)属于α-2肾上腺素能受体激动剂具有抗焦虑、催眠、镇痛和交感神经阻滞作用。最新研究发现右美托咪定对心脏和肺的缺血再灌注损伤具有显著的保护效应,但是右美托咪定是否对肠缺血再灌注损伤具有保护作用,迄今为止还没有相关研究。因此,本研究以小鼠为模型,观察右美托咪定预处理对小鼠肠缺血再灌注损伤的影响。方法:建立肠缺血再灌注损伤小鼠模型,并分为假手术组、缺血再灌注组和右美托咪定与处理组。不同剂量(10,25,50和100μg/kg)右美托咪定预处理小鼠。提取小鼠肠组织,用不同的试剂盒分别测定超氧化物歧化酶(Superoxide Dismutase,SOD),丙二醛(Malondialdehyde,MDA),谷胱甘肽(Glutathione,GSH),一氧化氮(Nitric Oxide,NO)和髓过氧化物酶(Myeloperoxidase,MPO)的水平变化。结果:右美托咪定预处理可以显著提高肠缺血再灌注损伤小鼠的存活率并呈剂量依赖性。右美托咪定预处理(100μg/kg)抑制由肠缺血再灌注损伤引起的不良效应,包括SOD水平降低,MDA水平升高,GSH水平降低,NO水平升高和MPO水平升高。结论:我们的研究表明右美托咪定可以提高小鼠肠缺血再灌注损伤的生存率,并且抑制氧化应激反应,炎症细胞的活化和侵润以及NO的水平,对肠缺血再灌注损伤具有显著的保护效应。本研究不仅进一步证实了右美托咪定的广泛的药理活性,而且为肠缺血再灌注损伤的治疗提供了潜在的治疗药物,其进一步的药理效应和作用机制值得进一步的研究。Objective： Dexmedetomidine belongs to α-2 adrenergic receptor agonist and processes a variety of pharmaceutical functions including anti-depression, hypnosis, analgesia and sympathetic block. Recently, dexmedetomidine has been demonstrated to have significant protective effect on myocardial and lung ischemia-reperfusion（I/R） injury. However, the role of Dexmedetomidine in intestinal I/R injury hasn＇t been explored to date. Thus, this study was to investigate the effect and mechanisms of dexmedetomidine pretreatment on intestinal I/R injury in mice. Methods： Intestinal model of ischemia/reperfusion injury was established, and the animals were divided into three groups： sham group, ischemia/reperfusion group and dexmedetomidine pretreatment group. Different doses of dexmedetomidine（10, 25, 50 and 100 μg/kg） were pre-administrated. Effects of dexmedetomidine on intestinal I/R injury was evaluated by myeloperoxidase（MPO）, superoxide dismutase（SOD）, malondialdehyde（MDA）, glutathione（GSH） and nitric oxide（NO） according to different kit protocol. Results： Dexmedetomidine improved survival rate of mice subjected to intestinal I/R injury in a dose-dependent manner. Dexmedetomidine pretreatment also attenuated the effects caused by I/R injury, which included decreased SOD and GSH and increased MDA and MPO. Conclusion： Our study demonstrated that dexmedetomidine shows protective effects on intestinal I/R injury in mice through modulation of oxidative stress, neutrophils infiltration and NO level. This study not only demonstrated the extensive pharmacological activities of dexmedetomidine,but also provided a potential therapeutic drug for intestinal I/R injury implying that the further protective effect and underlying mechanisms deserved further investigation.

关 键 词：右美托咪定 缺血再灌注损伤 氧化应激 

分 类 号：Q95-3[生物学—动物学] R574[医药卫生—消化系统]