联合应用环磷酰胺和超氧化物歧化酶对大鼠脑缺血-再灌注的保护作用

Protective effect of cyclophosphamide in combination with superoxide dismutase on cerebral ischemia/reperfusion injury in rats

目的探讨联合应用环磷酰胺与超氧化物歧化酶（SOD）对脑缺血-再灌注损伤模型大鼠的神经保护作用。方法取45只成年雄性Wistar大鼠，随机分为对照组、SOD组、环磷酰胺组及联合用药组，采用线栓法制作大鼠右侧大脑中动脉闭塞（MCAO）4h模型，剔除模型制作期间死亡的大鼠后，并补齐每组6只。经尾静脉给药，对大鼠脑缺血-再灌注模型进行干预，分别给予相应组别大鼠等渗盐水1．5ml、SOD2mg／kg、环磷酰胺100mg／kg及联合用药SOD1mg／kg＋环磷酰胺50mg／kg。给药时间为再灌注前20min、再灌注后12h和36h。MCAO期间及再灌注后48h记录大鼠脑组织血流量并计算相对值；再灌注后48h，进行神经功能缺损评分，并测定脑梗死相对体积。结果对照组、SOD组、环磷酰胺组和联合用药组的大鼠脑血流量变化相对值分别为（79±40）％、（81±19）％、（113±39）％和（134±43）％；神经功能缺损评分分别为4．7±0．7、4．5±0．5、4．3±0．7和3．7±0．8；脑梗死相对体积分别为4．3±1．0、3．1±0．9、2．3±0．8和2．0±0．6。所有观察指标，联合用药组与对照组比较，差异均有统计学意义（P〈0．01）；与SOD组或环磷酰胺组比较，差异也有统计学意义（P〈0．05）；SOD组或环磷酰胺组与对照组比较，除环磷酰胺组大鼠的脑血流量变化相对值增加外（P〈0．05），其余差异均无统计学意义（P〉0．05）。结论联合应用环磷酰胺与SOD对脑缺血-再灌注损伤模型大鼠的疗效较单独用药更加显著。

Objective To investigate the neuroprotective effect of cyclophosphamide in combination with superoxide dismutase （SOD） on cerebral ischemia/reperfusion injury in rats. Methods Twenty-four adult male Wistar rats were recruited and randomly allocated into one of the following four groups ： control, SOD, eyclophosphamide, and combination group （n = 6 in each group）. The rat model of fight middle cerebral artery occlusion （MCAO） for 4 hours was established by suture method. The cerebral ischemia/ reperfusion model rats were intervened via tail vein injection of isotonic saline 1.5 mL, SOD 2 mg, cyclophosphamide 100 mg, or SOD 1 mg/kg ＋ eyclophosphamide 50 mg/kg, respectively to the rats of corresponding groups, at 20 minutes before and 12 and 36 hours after reperfusion. The cerebral blood flow of rats were recorded during MCAO and at 48 hours after reperfusion, and the relative values were calculated; the neurological scores was evaluated at 48 hours after reperfusion, and the relative values of cerebral infarction were detected by triphenyltetrazolium chloride （TTC） staining. Results The relative values of cerebral blood flow changes of rats in the control, SOD, cyclophosphamide, and combination groups were 79 ±40% , 81 ± 19% , 113 ±39% , and 134 ±43% , respectively; the neurological deficit scores were 4. 7± 0. 7, 4.5 ±0. 5, 4. 3 ± 0. 7, and 3.7 ± 0. 8, respectively ; and the relative values of cerebral infarction were 4. 3 ± 1.0, 3. 1 ± 0. 9, 2. 3± 0. 8, and 2. 0 ± 0. 6, respectively. There were significant significances between the combination group and control group in all the observation indices （P 〈 0. 01 ） ; as compared with the SOD group or cyclophosphamide group, there was also significant significance （P 〈 0. 05） ; as compared between the control group and the SOD group or cyclophosphamide group there was no statistical significance, except the relatirely increased value of cerebral blood flow in the cyclophosphamide group （ P 〉 0. 05）. Conclusion The therapeutic efficacy of cyclophosphamide in combination with SOD is more significant than single medication in the rat model of ischemia/repeffusion injury.