右美托咪定后处理联合肢体缺血后处理对大鼠心肌缺血再灌注损伤的影响

Effect of dexmedetomidine postconditioning combined with limb ischemic postconditioning on myocardial ischemia-reperfusion injury in rats

目的评价右美托咪定后处理联合肢体缺血后处理对大鼠心肌缺血再灌注损伤的影响。方法雄性sD大鼠50只，2～3月龄，体重275～335g，采用随机数字法分为5组（n=10）：假手术组（S组）、缺血再灌注组（I／R组）、右美托咪定后处理组（DP组）、肢体缺血后处理组（LP组）和右美托咪定后处理联合肢体缺血后处理组（DLP组）。采用结扎大鼠左冠状动脉前降支30min，再灌注180min的方法制备心肌缺血再灌注损伤模型。于再灌注前15min时，DP组和DLP组腹腔注射右美托咪定50μg／kg，I／R组和LP组腹腔注射生理盐水0．5ml；LP组和DLP组于再灌注前10min时，用止血带结扎大鼠双后肢10min，然后恢复灌注。于再灌注180min时，取颈内动脉血样，测定血浆CK—MB和谷胱甘肽过氧化物酶（GSH—Px）的活性、cTnI、MDA、IL-1β、IL-6和TNF-α的浓度；取心肌组织，测定心肌梗死体积。结果与s组比较，I／R组、DP组、LP组和DLP组血浆CK—MB活性和cTnI浓度升高，心肌梗死体积升高，血浆MDA、TNF-α、IL-1D和IL-6的浓度升高，GSH—Px活性降低（P〈0．05）；与I／R组比较，DP组、LP组和DLP组血浆CK—MB活性和cTnI浓度降低，心肌梗死体积降低，血浆MDA、TNF-α、IL-1β和IL一6的浓度降低，GSH—Px活性升高（P〈0．05）；与DP组和LP组比较，DLP组血浆CK—MB活性和cTnI浓度降低，心肌梗死体积降低，血浆MDA、TNF-α、IL-1β和IL一6的浓度降低，GSH—Px活性升高（P〈O．05）。结论右美托咪定后处理联合肢体缺血后处理可减轻大鼠心肌缺血再灌注损伤，且效果优于两者单独应用，其机制可能与抑制脂质过氧化反应和全身炎性反应有关。

Objective To evaluate the effect of dexmedetomidine postconditioning combined with limb ischemic postconditioning on myocardial ischemia-reperfusion （I/R） injury in rats. Methods Fifty male Sprague-Dawley rats, aged 2-3 months, weighing 275-335 g, were randomly divided into 5 groups （n = 10 each） using a random number table： sham operation group （group S） ; I/R group; dexmedetomidine posteonditioning group （group DP） ; limb ischemie posteonditioning group （group LP） ; dexmedetomidine posteonditioning combined with limb ischemic postconditioning group （group DLP）. Myocardial I/R was induced by occlusion of the left anterior descending branch of coronary artery for 30 min followed by 180 min reperfusion. At 15 min before reperfusion, dexmedetomidine 50ug/kg was injected intraperitoneally in DP and DLP groups, while normal saline 0.5 ml was injected intraperitoneally in I/R and LP groups. In LP and DLP groups, the animals underwent 10 min ischemia of bilateral hind limbs starting from l0 min before reperfusion, followed by reperfusion. Blood samples were taken from the internal carotid artery at 180 min of reperfusion for determination of the plasma ereatine kinase-MB （CK-MB） and glutathione peroxidase （GSH-Px） activities and the concentrations of cardiac troponin I （cTnI）, malondialdehyde （MDA）, interleukin-lbeta （IL-1β）, IL-6 and tumor necrosis factor-alpha （TNF-α）. Myocardial specimens were obtained at 180 min of reperfusion for determination of the myocardial infarct size. Results Compared with group S, the plasma CK-MB activity, myocardial infarct size and plasma cTnI, MDA, TNF-α, IL-Iβ and IL-6 concentrations were significantly increased, and GSH-Px activity was significantly decreased in I/R, DP, LP and DLP groups （P〈0.05）. Compared with group I/R, the plasma CK-MB activity, myocardial infarct size and plasma cTnI, MDA, TNF-α, IL-Iβ and IL-6 concentrations were significantly decreased, and the GSH-Px activity was significantly increased in DP, LP and DLP groups （P〈0.05）. Compared with DP and LP groups, the plasma CK-MB activity, myocardial infarct size and plasma cTnI, MDA, TNF-α, IL-Iβ and IL-6 concentrations were significantly decreased, and the GSH-Px activity was significantly increased in group DLP （P〈 0.05）. Conclusion Dexmedetomidine postconditioning combined with limb ischemic postconditioning provides better efficacy than either alone in reducing the myocardial I/R injury in rats, and the mechanism may be related to the inhibition of lipid peroxidation and systemic inflammatory responses.