联合应用尼莫地平和胞磷胆碱对大鼠局灶性脑缺血的神经保护作用被引量：2

Neuroprotective effect of the combination of nimodipine and citicoline on focal cerebral ischemia-reperfusion in rats

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摘要目的探讨联合应用尼莫地平、胞磷胆碱对局灶性脑缺血-再灌注大鼠的脑保护作用。方法Sprague-Dawley雄性大鼠48只,随机分为缺血对照组,尼莫地平组,胞磷胆碱组及联合用药组,每组12只。线栓法制作大脑中动脉栓塞90min,同侧颈总动脉结扎60min模型。尼莫地平经颈内动脉给药（40μg/kg）;胞磷胆碱经腹腔注射给药（250mg/kg,1次/d,连用3d）。再灌注后24h行神经功能缺损评分;再灌注后72h测量脑组织梗死体积,采用流式细胞仪检测大鼠前脑皮质细胞凋亡率。结果对照组、尼莫地平组、胞磷胆碱组及联合用药组神经功能缺损评分分别为2.6±0.8、1.5±1.2、1.2±0.8和0.7±0.6;脑梗死体积分别为（186±25）、（122±22）、（119±21）和（81±27）mm^3;细胞凋亡率分别为（30.6±1.9）、（8.8±2.0）、（4.6±2.4）、（2.2±1.7）%。所有观察指标,用药组与对照组比较,差异均有统计学意义（P〈0.05）;尼莫地平组与胞磷胆碱组相比,无统计学意义（P〉0.05）;联合用药组与尼莫地平组或胞磷胆碱组比较,差异有统计学意义（P〈0.05）。HE染色显示,所有用药组神经细胞缺血性损伤较对照组明显减轻。结论脑缺血-再灌注后,尼莫地平和胞磷胆碱早期使用均有效,两药联合使用疗效优于单独用药。 Objective To investigate the neuroprotective effect of the combination of nimodipine and citicoline on focal cerebral ischemia-repeffusion injury in rats. Methods Forty-eight male Sprague-Daw- ley rats were randomly and evenly allocated into ischemic control, nimodipine, citicoline, and combined medication groups. A model of middle cerebral artery occlusion （MCAO） for 90 min was established by the suture method, and ipsilateral common carotid artery was ligated for 60 rain. Intracarotid infusion of nimo- dipine was administered （40 μg/kg） ; citicoline was injected intraperitoneally （250 mg/kg）. The neuro- logical deficit scores were performed 24 hours after reperfusion; the cerebral infarct volumes were measured 72 hours after reperfusion. The apoptosis rates of the forebrain cortex were detected by flow cytometry. Results The neurological deficit scores in the ischemic control, nimodipine, citicoline and combined medication groups were 2.6 ± 0.8, 1.5 ± 1.2, 1.2 ± 0.8, and 0.7 ± 0.6, respectively ; their cerebral in- farct volumes were 186 ± 25, 122 ± 22, 119 ± 21, and 81 ± 27 mm^3 , respectively;and their apoptosis rates were 30.6 ± 1.9, 8.8 ± 2.0, 4.6 ± 2.4, and 2.2 ± 1.7% , respectively. There were significant differences between the drug treatment groups and the control group in all the outcome indexes （ P 〈 0.05 ）. There was no significant difference between the nimodipine group and the citicoline group （ P 〉 0.05 ）.There were significant differences between the combined medication group and the nimodipine or citicoline alone groups （P 〈 0.05）. tiE staining showed that the ischemic neuronal damages in all the drug treatment groups were obviously milder than those in the control group. Conclusions Early use of both nimodipine and citicoline after cerebral ischemia-reperfusion is effective. The combination of nimodipine and citicoline has synergistic neuroprotective effect, and its efficacy is better than any one alone.