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丁咯地尔在大鼠中度脑缺血模型中的保护作用。

Protective effect of buflomedil in a rat model of moderate cerebral ischemia.

作者信息

Briguglio Francesco S, Mondello Maria Rita, Galluzzo Mariangela, Raneri Eugenio, De Pasquale Anna, Saija Antonella, Trombetta Domenico

机构信息

Dipartimento Farmaco-Biologico, School of Pharmacy, University of Messina, Italy.

出版信息

Arzneimittelforschung. 2005;55(8):437-42. doi: 10.1055/s-0031-1296885.

Abstract

Buflomedil hydrochloride (CAS 55837-25-7) is a vasoactive drug with a variety of pharmacodynamic properties. Although a number of studies have been carried out to verify the beneficial effect of buflomedil in ischemic peripheral conditions, few data are reported to justify the efficacious employment of buflomedil in the treatment of cerebrovascular diseases. The aim of the present study was to better investigate the neuroprotective effect of buflomedil in normal pentobarbital-anaesthetized rats subjected to transient bilateral common artery occlusion (BCO) for 20 min. Buflomedil hydrochloride (10 mg/kg) was administered by slow intravenous infusion (90 min), starting 1 h after the onset of ischemia. The rats were sacrificed 48 h after carotid clamping. BCO caused dramatic death of hippocampal CA1 pyramidal neurons, and a significant increase in circulating levels of neuron-specific enolase (NSE) and lactate. Treatment with buflomedil attenuated ischemia-induced histological loss and damage of CA1 pyramidal cells. Furthermore, in ischemic rats, the drug restored blood lactate concentrations and serum NSE concentrations to near normal levels. These data clearly demonstrate that buflomedil is able to protect brain neurons against damage following moderate global cerebral ischemia. One could speculate that this protective effect could be related to the capability of buflomedil to improve cerebral blood flow and energy metabolism, or to a smooth muscle relaxant effect on cerebral blood vessels.

摘要

盐酸丁咯地尔(CAS 55837-25-7)是一种具有多种药效学特性的血管活性药物。尽管已经开展了多项研究来验证丁咯地尔在缺血性外周疾病中的有益作用,但鲜有数据表明丁咯地尔在治疗脑血管疾病方面的有效应用。本研究的目的是更好地研究丁咯地尔对正常戊巴比妥麻醉的大鼠短暂双侧颈总动脉闭塞(BCO)20分钟后的神经保护作用。盐酸丁咯地尔(10mg/kg)在缺血开始1小时后开始通过缓慢静脉输注(90分钟)给药。在颈动脉夹闭48小时后处死大鼠。BCO导致海马CA1锥体神经元大量死亡,神经元特异性烯醇化酶(NSE)和乳酸的循环水平显著升高。丁咯地尔治疗减轻了缺血诱导的CA1锥体细胞的组织学损失和损伤。此外,在缺血大鼠中,该药物将血乳酸浓度和血清NSE浓度恢复到接近正常水平。这些数据清楚地表明,丁咯地尔能够保护脑神经元免受中度全脑缺血后的损伤。可以推测,这种保护作用可能与丁咯地尔改善脑血流量和能量代谢的能力有关,或者与对脑血管的平滑肌舒张作用有关。

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