预先鞘内注射右美托咪定对大鼠心肌缺血再灌注损伤的影响

Effect of intrathecal dexmedetomidine pretreatment on myocardial ischemia-reperfusion injury in rats

目的探讨预先鞘内注射右美托咪定对大鼠心肌缺血再灌注损伤的影响。方法取鞘内置管成功的成年SD大鼠45只，雌雄不拘，体重200-250 g，采用随机数字表法分为3组（n＝15）：假手术组（S组）、心肌缺血再灌注组（I/R组）和预先鞘内注射右美托咪定组（DEX组）。采用结扎冠状动脉左前降支30 min、再灌注120 min的方法制备心肌缺血再灌注损伤模型。DEX组于缺血前30 min鞘内注射右美托咪定1 μg/kg（用生理盐水稀释至10 μl）。于再灌注120 min时，心尖部采集血样2 ml，测定血浆NE和cTnI浓度，然后处死大鼠，取心肌组织，计算心肌梗死体积；取脊髓组织，采用Western blot法检测脊髓背角c-fos表达水平。结果与S组比较，I/R组和DEX组心肌梗死体积和血浆NE、cTnI浓度升高，脊髓背角c-fos表达上调（P〈0.05）；与I/R组比较，DEX心肌梗死体积和血浆NE、cTnI浓度降低，脊髓背角c-fos表达下调（P〈0.05）。结论预先鞘内注射右美托咪定可减轻大鼠心肌缺血再灌注损伤，其机制可能与降低血浆NE水平，抑制脊髓背角c-fos表达有关。

Objective To investigate the effect of intrathecal dexmedetomidine pretreatment on myocardial ischemia-reperfusion （I/R） injury in rats.Methods Forty-five adult Sprague-Dawley rats of both sexes, weighing 200-250 g, in which intrathecal catheters were successfully placed without complications, were divided into 3 groups （n=15 each） using a random number table： sham operation group （group S）, group I/R and intrathecal dexmedetomidine pretreatment group （group DEX）. Myocardial I/R injury was produced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.Dexmedetomidine 1 μg/kg （diluted to 10 μl in normal saline） was intrathecally injected at 30 min before ischemia in group DEX.The equal volume of normal saline was given in group I/R.Blood samples were collected from the cardiac apex at the end of reperfusion for measurement of plasma norepinephrine （NE） and cardiac troponin I （cTnI） concentrations.Then all the rats were sacrificed, and myocardial tissues were obtained for determination of myocardical infarct size, and the spinal cord was isolated to detect the expression of c-fos in the spinal dorsal horn by Western blot. ResultsCompared with group S, the myocardical infarct size, plasma NE and cTnI concentrations were significnatly increased, and the expression of c-fos in the spinal dorsal horn was up-regulated in I/R and DEX groups （P〈0.05）. Compared with group I/R, the myocardical infarct size, plasma NE and cTnI concentrations were significnatly decreased, and the expression of c-fos in the spinal dorsal horn was down-regulated in group DEX （P〈0.05）.Conclusion Intrathecal dexmedetomidine pretreatment can reduce myocardial I/R injury in rats, and the mechanims may be related to decreasing plasma NE levels and inhibiting c-fos expression in the spinal dorsal horn.