右美托咪定预先给药对大鼠肢体缺血-再灌注诱发心肌损伤的影响

Effects of dexmedetomidine pretreatment on myocardial injury induced by ischemia-reperfusion of hind limbs in rats

目的探讨右美托咪定预先给药对肢体缺血-再灌注大鼠诱发心肌损伤的影响。方法健康清洁级SD大鼠30只,6周龄,体重200～250g,采用随机数字表法,将大鼠分为三组,每组10只：假手术组（S组）,仅分离股动脉和股静脉;缺血-再灌注组（IR组）;右美托咪定预先给药组（D组）。采用无创微动脉夹夹闭股动脉4h后恢复双后肢血流灌注4h的方法制备动物模型。D组肢体缺血前30min腹腔注射右美托咪定50μg/kg,S组和IR组腹腔注射等容量生理盐水。再灌注结束前15min经颈动脉行左心室插管,测量再灌注4h时各组动物左心室收缩压（LVSP）、左室舒张末压（LVEDP）、左室内压最大上升速率（＋dp/dtmax）和左室内压最大下降速（-dp/dtmax）。实验结束时自腹主动脉取血,测定血浆SOD活性和MDA含量。开胸取心肌组织,测定心肌组织SOD活性和MDA含量,光镜下观察心肌病理学改变。结果与S组比较,IR组、D组血浆和心肌组织SOD活性明显降低,MDA含量明显升高（P〈0.05）;与IR组比较,D组血浆和心肌组织SOD活性明显升高,MDA含量明显降低（P〈0.05）。与S组比较,IR组、D组LVSP、＋dp/dtmax、-dp/dtmax明显降低,LVEDP明显升高（P〈0.05）;与IR组比较,D组LVSP、＋dp/dtmax、-dp/dtmax明显升高,LVEDP明显降低（P〈0.05）。与IR组比较,D组心肌病理学结果显示损伤减轻。结论右美托咪定预先给药可减轻大鼠肢体缺血-再灌注诱发的心肌损伤,其机制可能与减轻心肌脂质过氧化反应和改善心肌血流灌注有关。

Objective To evaluate the effects of dexmedetomidine pretreatment on myocardial injury induced by ischemia-reperfusion（IR）of hind limbs in rats.Methods Thirty healthy SpragueDawley rats,weighing 200-250 g,were randomly divided into 3groups（n=10,each）：group sham operation（group S）,group IR and group dexmedetomidine pretreatment（group D）.Limb ischemia was induced by occlusion of bilateral hind limbs for 4hfollowed by reperfusion for 4hin group IR and group D.Dexmedetomidine 50μg/kg was injected intraperitoneally 30 min before reperfusion of hind limbs in group D,while equal volume of normal saline was injected in group S and group IR.The rats were sacrificed at 4hof reperfusion and myocardial specimens were obtained for microscopic examination of pathologic changes and for determination of superoxide dismutase（SOD）activity and malondialdehyde（MDA）content in myocardial tissues.Left ventricular systolic pressure（LVSP）,left ventricular end diastolic pressure（LVEDP） and ± dp/dtmax were measured and recorded.Results Compared with group S,MDA content was significantly increased,and SOD activity was decreased in group IR and D（P〈0.05）.Compared with group IR,MDA content was significantly decreased and SOD activity was increased（P〈0.05）.Compared with group S,LVSP,±dp/dtmax were significantly decreased and LVEDP was increased in group IR and group D（P〈0.05）.Compared with group IR,LVSP,±dp/dtmax were significantly increased and LVEDP was decreased in group D（P〈0.05）.The pathological changes were significantly attenuated in group D compared with group IR.Conclusion Dexmedetomidine pretreatment can reduce myocardial injury induced by IR of hind limbs in rats and the mechanism may be related to inhibition of lipid peroxidation and increasein the blood flow of myocardium.