Memantine对大鼠局灶性脑缺血损伤的长期神经保护效应

目的：探讨N-甲基-D-天门冬氨酸盐（NMDA）受体拮抗剂美金刚（MEM）对大鼠局灶性脑缺血损伤的长期神经保护作用.方法：将70只SD大鼠随机分为假手术组（n=6）和对照组,MEM5,10,20mg/kg组（n=16）.除假手术组外,其余各组动物均行线栓法阻闭大脑中动脉（MCAO）120min.MEM各组分别在脑缺血后15min腹腔注射MEM5,10,20mg/kg,对照组在脑缺血后15min腹腔注射等容积生理盐水.再灌注7d后进行神经功能评分,处死动物后行2,3,5-氯化三苯四唑（TTC）染色,测定脑梗死容积百分比,酶联免疫法检测脑组织肿瘤坏死因子α（TNFα）,白细胞介素-6（IL-6）含量.结果：再灌注7d后,神经功能评分MEM10,20mg/kg组均明显优于对照组,MEM20mg/kg组优于MEM10mg/kg组（P〈0.01）,MEM5mg/kg组与对照组相比较差异无显著性.脑梗死容积MEM10,20mg/kg组明显小于对照组,MEM20mg/kg组小于MEM10mg/kg组（P〈0.01）,MEM5mg/kg组与对照组相比较差异无统计学意义.脑组织中炎症因子TNFα,IL-6含量对照组较假手术组显著升高（P〈0.01）,MEM10,20mg/kg组较对照组明显降低（P〈0.01）.MEM5mg/kg组较对照组TNFα,IL-6含量差异无统计学意义.结论：MEM对大鼠局灶性脑缺血损伤有长期神经保护效应,此神经保护效果呈剂量依赖性,其机制可能与降低脑组织TNFα,IL-6含量相关.

Long-term neuroprotective effects of memantine on focal cerebral ischemia in rats

AIM:To evaluate the long-term neuroprotective effects of memantine(MEM)on transient focal cerebral ischemic injury in rats.METHODS:Seventy male Spraque-Dawley rats were radomly divided into sham(n=6),control(n=16),MEM 5(n=16),MEM 10(n=16)and MEM 20(n=16)groups.Each group except sham group were subjected to focal cerebral ischmia induced by middle cerebral artery occlusion(MCAO)for 2 h.MEM 5,MEM 10 and MEM 20 groups were administered intraperitoneally memantine 5,10 and 20 mg/kg respectively 15 min after foc...