Memantine对大鼠局灶性脑缺血损伤的长期神经保护效应

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

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.

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 focal cerebral ischemia.Control group were administered intraperitoneally normal saline of the same volume as memantine groups 15 min afterfocal cerebral ischemia.After 7 d period of reperfusion,the animals were examined for neurological behavior scores and then killed to measure the infarct volumes and the content of TNFα and IL-6.RESULTS：The neurological bebavior scores were better in MEM 10 and MEM 20 groups than those in control group,and the neurological score was better in MEM 20 group than that in MEM 10 group,but no statistical difference was found between MEM 5 group and control group.The infarct volumes in MEM 10（27.06±6.6）% and MEM 20 groups（21.32±10.76）% were significantly smaller than those in control group（41.3±6.48）%（P〈0.01）,and the infarct volume in MEM 20 group significantly smaller than that in MEM 10 group（P〈0.01）,but no statistical difference was found between MEM 5（35.98±11.07）% and control group.The contents of TNFα and IL-6 were significantly increased in control group compared with those in sham group（P〈0.01）.The contents of TNFα and IL-6 were signaficantly decreased in MEM 10 group（5.72±0.60）,（135.33±9.80）μg/L and MEM 20 group（5.28±0.66）,（123.67±8.60）μg/L compared with those in control group（P〈0.01）.There is no statistical differences between MEM 5 group and control group.CONCLUSION：Memantine has long-term neuroprotective effects against focal cerebral ischemic injury in a dose-dependent manner and the neuroprotective mechanism may be related to reducing the levels of TNFα and IL-6 in brain tissues.