选择性β1肾上腺素受体阻滞剂艾司洛尔及兰地洛尔对大鼠脊髓缺血和再灌注损伤的神经保护作用

背景在胸科手术及胸腹部大动脉手术中，截瘫时有发生，它是一种严重的不可预料的并发症。由于超短效选择性β1-肾上腺素受体阻滞剂能在脑缺血后提供神经保护作用，因此我们推断：它们也能减轻大鼠短暂性脑缺血和再灌注所引起的脊髓损伤。方法将雄性Sprague．Dawley鼠随机分成四组：生理盐水组（以0．5ml／L速率静脉输注0．9％盐水，n=8）、艾司洛尔组（200μg．kg^-1·min^-1，n=8）、兰地洛尔组（50μg·kg^-1·min^-1）或假手术组（n=6）。从脊髓缺血前30分钟开始输注生理盐水或药物，并持续到再灌注后24小时。通过主动脉内球囊阻塞联合持续近端动脉低血压10分钟的方法来建立脊髓缺血模型，然后对脊髓进行24小时再灌注。缺血性损伤程度是通过再灌注24小时后的后肢运动损伤指数分数和位于脊髓前角的有活力的运动神经细胞数量来进行评估的。结果艾司洛尔组及兰地洛尔组的运动损伤指数分数较生理盐水组显著性降低（P〈0．05）。组织病理学评估发现艾司洛尔组及兰地洛尔组的脊髓损伤程度较生理盐水组轻（P〈0．05）。结论上述结果显示超短效选择性β1-肾上腺素受体阻滞剂能在大鼠脊髓缺血一再灌注损伤模型中减轻神经损伤。

BACKGROUND： Paraplegia is a devastating and unpredictable complication occasionally resulting from sur- gery of the thoracic and thoracoabdominal aorta. Because ultrashort-acting selective βl-adrenoreceptor antagonists provide neuroprotective effects after brain ischemia, we hypothesized that they would also ameliorate spinal cord injury after transient ischemia and reperfusion in rats. METHODS： Male Sprague-Dawley rats were randomly assigned to one of the following 4 groups： saline （received IV infusion of 0.9% saline at a rate of 0.5 ml/h, n = 8）, esmolol （esmolo1200μg/kg/min, n = 8）, landiolol （landiolo150 μg/kg/min）, or sham surgical （n = 6）. Infusion of saline or drugs was initiated 30 minutes before spi- nal cord ischemia and continued for the subsequent 24-hour reperfusion. Spinal cord ischemia was induced by intraaortic bal- loon occlusion combined with proximal arterial hypotension for 10 minutes. The spinal cord was then reperfused for 24 hours. Ischemic injury was assessed in terms of the motor deficit index score of the hindlimb and the number of viable motor nerve cells in the anterior spinal cord at 24 hours after reperfusion. RESULTS： The motor deficit index scores were signifi- cantly lower in the esmolol and landiolol groups compared with the saline group （P 〈 0. 05 ）. Histopathologic evaluation of the spinal cord showed less damage in the esmolol and landiolol groups than in the saline group （P 〈 0.05）. CONCLU- SIONS： These data show that ultrashort-acting selective β1-adrenoreceptor antagonists can reduce neurological injury in a rat model of spinal cord ischemia-reperfusion.