尼莫地平和超氧化物歧化酶联合抗缺血/再灌注损伤作用研究

The neuroprotective effects of combined nimodipine and superoxide dismutase on cerebral ischemia/reperfusion in rats

目的研究尼莫地平和超氧化物歧化酶(superoxide dismutase,SOD)联合治疗大鼠脑缺血/再灌注损伤的神经保护作用。方法将45只成年雄性Wistar大鼠随机分成4组,尼莫地平组、超氧化物歧化酶组、联合药物(尼莫地平加超氧化物歧化酶)组和对照组。应用线栓法制作大鼠MCAO模型,缺血后4h行再灌注。于再灌注前20min、再灌注后12h和36h尾静脉给药;48h后计算大鼠存活率、行神经功能缺损评分、脑血流量和脑梗死体积测定。结果①大鼠存活率分别为:41.7%、27.3%、70.0%和25.0%。联合药物组较对照组的存活率明显增加(P<0.05)。②神经功能缺损评分为:4.39±0.197、4.47±0.492、3.79±0.521和4.67±0.709。联合药物组较对照组的神经功能缺损明显减少(P<0.01),较尼莫地平或SOD组也明显减少(P<0.05)。③脑组织血流量为:96±23%、81±19%、129±47%和79±41%。与对照组相比三个药物组的脑血流量均增加(P<0.05)。联合药物组的脑血流量增加又明显高于单药治疗组(P<0.05)。④梗死体积为:261.0±55.2、261.2±59.3、128.5±58.4和383.5±58.8mm3。联合药物组梗死体积明显小于对照组(P<0.05)和两个单药组(P<0.01,P<0.05)。结论尼莫地平和超氧化物歧化酶联合用药对脑缺血/再灌注损伤具有神经保护作用,并且优于单一药物治疗。

Objective To investigate the effects of the combination therapy of nimodipine with superoxide dismutase for reperfusion injury after focal cerebral ischemia in rats. Methods Forty-five adult male Wistar rats were randomly divided into 4 groups, nimodipine, superoxide dismutase, nimodipine plus superoxide dismutase and control groups. A rat model of middle cerebral artery occlusion （MCAO） was induced by the intraluminal suture method; Reperfusion was performed 4 hours after cerebral ischemia. At 20 minutes before reperfusion after cerebral ischemia, 12 h and 36 h after reperfusion, the medications were injected slowly into the tail veins of rats. The survival rate of rats was calculated 48 hours after cerebral ischemia/reperfusion, and the volumes of cerebral infarction and neurological deficit scores were measured. Results ① The survival rate of rats in the four groups were 41.7%, 27.3%, 70.0% and 25%, respectively. The survival rate in nimodipine plus superoxide dismutase group is higher than that in the control group （P〈0.05）. ② Neurological deficit scores were 4.39±0.197, 4.47±0.492, 3.79±0.521 and 4.67±0.709, respectively. Neurological deficit scores in nimodipine plus superoxide dismutase group were less than those in the control group （P〈0.01） and the other two medication groups （P〈0.05）. ③ Cerebral blood flow in rats was 96±23%, 81±19.457%, 129±47.053% and 79±40.533%, respectively. In comparison to the other medication groups, the nimodipine plus superoxide dismutase group has a higher cerebral blood flow （P〈0.05）. ④ The volumes of cerebral infarction in rats were 261.20±55, 261.17±59, 128.53±58and 383.50±59mm3, respectively. The volumes of cerebral infarction in nimodipine plus superoxide dismutase group was less than control group （P〈0.05） and the other 2 medication groups （P〈0.01, P〈0.05, respectively）. Conclusion The neuroprotective effects of combination of nimodipine and superoxide dismutase on focal cerebral ischemia/reperfusion injury in rats were better than the single of the two medications.