In this study we investigated the neuroprotective efficacy of dexmedetomidine (Dex) and phosphocreatine (PCr) alone or in combination in a rat model of focal cerebral ischemia-reperfusion injury (I/R). I/R was induced by intraluminal middle cerebral artery occlusion (MCAO) and reperfusion. Male Sprague-Dawley rats were randomly allocated to the Sham group and I/R group, and the I/R group was further divided into three subgroups: Dex (9 μg.kg⁻¹ Dex), PCr (180 mg.kg⁻¹ PCr) and Dex + PCr (9 μg.kg⁻¹ Dex + 180 mg.kg⁻¹ PCr). All treatments were given intravenously at the onset of reperfusion. After 24 hr of reperfusion, the neurological deficit score (NDS) was determined and a magnetic resonance imaging (MRI) scan was performed. Serum concentrations of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured and cerebral infarct volume was estimated by triphenyl tetrazolium chloride (TTC) staining. Blood brain barrier, neuronal and mitochondrial damage was assessed by optical and electron microscopy. Neuronal injury was further assessed using double cleaved caspase-3 and NeuN immunofluorescent staining. Compared with group I/R, Dex and PCr significantly reduced the neurological deficit score (P < 0.01), infarct volume (P < 0.01), and brain blood barrier, neuronal and mitochondrial damage. The level of oxidative stress (P < 0.001) and neuronal injury (P < 0.001) also decreased and surviving neurons increased (P < 0.001). Compared with Dex or PCr alone, the combination treatment had overall greater effects (P < 0.05). These results indicate that posttreatment with Dex or PCr decreases focal cerebral I/R injury and that these agents in combination have greater protective effects than each alone.

在这项研究中，我们研究了右美托咪定 (Dex) 和磷酸肌酸 (PCr) 单独或组合在局灶性脑缺血再灌注损伤 (I/R) 大鼠模型中的神经保护功效。I/R 是由腔内大脑中动脉闭塞 (MCAO) 和再灌注引起的。雄性Sprague-Dawley大鼠随机分为Sham组和I/R组，I/R组又分为三个亚组：Dex（9 μg.kg ⁻¹ Dex）、PCr（180 mg.kg ⁻¹ PCr) 和 Dex + PCr (9 μg.kg ⁻¹ Dex + 180 mg.kg ⁻¹聚合酶链反应）。所有治疗均在再灌注开始时静脉内给予。再灌注 24 小时后，确定神经功能缺损评分 (NDS) 并进行磁共振成像 (MRI) 扫描。测量丙二醛 (MDA) 和 4-羟基壬醛 (4-HNE) 的血清浓度，并通过氯化三苯基四唑 (TTC) 染色估计脑梗塞体积。通过光学和电子显微镜评估血脑屏障、神经元和线粒体损伤。使用双裂 caspase-3 和 NeuN 免疫荧光染色进一步评估神经元损伤。与 I/R 组相比，Dex 和 PCr 显着降低了神经功能缺损评分（P < 0.01）、梗死体积（P < 0.01）以及脑血屏障、神经元和线粒体损伤。氧化应激水平 (P < 0. 001) 和神经元损伤 (P < 0.001) 也减少，存活的神经元增加 (P < 0.001)。与单独使用 Dex 或 PCr 相比，联合治疗的总体效果更好（P < 0.05）。这些结果表明用 Dex 或 PCr 进行后处理可减少局灶性脑 I/R 损伤，并且这些药物联合使用比单独使用具有更大的保护作用。