Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Akita, Japan.
Brain Res. 2010 Jul 9;1343:213-7. doi: 10.1016/j.brainres.2010.04.079. Epub 2010 May 6.
We have reported the neuroprotective effects of pre-treatment with beta-adrenoceptor antagonists on the cerebral infarction at 1 and 7 days after focal ischemia in rats. However, the protective effect of post-treatment with beta-adrenoceptor antagonists has not been investigated yet. This study was conducted to evaluate the post-treatment effects of selective beta(1)-adrenoceptor antagonists in the rat focal cerebral ischemia. Halothane anesthetized, normothermic adult male Sprague-Dawley rats were subjected to 2h of middle cerebral artery occlusion (MCAO) using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received intravenous infusion of saline 0.5 mL/h, esmolol 200 microg/kg/min, or landiolol 50 microg/kg/min (n=8 in each group). Infusion was initiated 30 min after MCAO and continued for 24h. Rats were allowed to survive for 7 days, and the neurological deficit score was evaluated at 1, 4 and 7 days after reperfusion. The brains were removed and stained with triphenyltetrazolium chloride at 7 days after reperfusion. Neurological deficit scores were lower in the rats treated with esmolol or landiolol, compared with saline-treated rats at 1 day as well as 4 and 7 days. The infarct volumes of cortical and striatum were less in the rats receiving beta-adrenoceptor antagonists than in saline-treated rats (P<0.05). The current study indicates that administration of selective beta1-adrenoceptor antagonists after the onset of ischemia also improved neurological and histological outcomes following transient focal cerebral ischemia in rats.
我们曾报道过预先给予β-肾上腺素受体拮抗剂对大鼠局灶性缺血后 1 天和 7 天的脑梗死的神经保护作用。然而,β-肾上腺素受体拮抗剂的后期治疗作用尚未得到研究。本研究旨在评估选择性β1-肾上腺素受体拮抗剂在大鼠局灶性脑缺血中的后期治疗效果。使用激光多普勒血流仪证实的腔内缝线技术,对异氟烷麻醉、体温正常的成年雄性 Sprague-Dawley 大鼠进行 2 小时的大脑中动脉闭塞(MCAO)。大鼠接受 0.5ml/h 的生理盐水、艾司洛尔 200μg/kg/min 或拉贝洛尔 50μg/kg/min 的静脉输注(每组 8 只)。输注在 MCAO 后 30 分钟开始,并持续 24 小时。大鼠允许存活 7 天,并在再灌注后 1、4 和 7 天评估神经功能缺损评分。在再灌注后 7 天用三苯基四氮唑氯化物染色取出大脑。与生理盐水处理的大鼠相比,接受艾司洛尔或拉贝洛尔治疗的大鼠在 1 天以及 4 天和 7 天都具有更低的神经功能缺损评分。接受β-肾上腺素受体拮抗剂治疗的大鼠皮质和纹状体的梗死体积小于生理盐水处理的大鼠(P<0.05)。目前的研究表明,在缺血发作后给予选择性β1-肾上腺素受体拮抗剂也能改善大鼠短暂性局灶性脑缺血后的神经和组织学结果。