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N-甲基-D-天门冬氨酸受体-1反义寡核苷酸对大鼠脑缺血性损伤的保护作用 被引量：2

Neuroprotective effects of NMDAR1 antisense oligodeoxynucleotides on focal cerebral ischemic injury in rats
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摘要 目的探讨N-甲基-D-天门冬氨酸受体1(NMDAR1)反义寡核苷酸(ASODN)对局灶性脑缺血再灌注损伤后的影响。方法将90只雄性Wistar大鼠随机分为3组:缺血再灌注组30只:采用Longa改良方法制作大鼠可复流大脑中动脉闭塞(MCAO)模型,在缺血2h后进行再灌注;对照组30只:MCAO模型成功后立即向侧脑室内注入10μl灭菌PBS,在缺血2h后进行再灌注;ASODN组30只:MCAO模型成功后立即向侧脑室注入10μlNMDAR1反义寡核苷酸。以上3组依缺血2h后再灌注时间0、6、24、48、72h分为5个亚组,除再灌注72h时间点10只外,其余每个亚组5只。在相应时间点取脑,行HE染色、NMDAR1免疫组织化学检测及脑梗死体积测定。结果ASODN组神经功能缺损评分(1.4±0.5)显著低于缺血再灌注组(2.4±0.6)和对照组(2.5±0.4),P<0.05;ASODN组缺血周边区NMDAR1阳性细胞数(36±10)显著少于缺血再灌注组(46±20)和对照组(50±16),P<0.05。ASODN组平均脑梗死体积百分比(28±4)%显著低于缺血再灌注组(42±3)%和对照组(43±5)%,P<0.01。结论局灶性脑缺血后侧脑室内注入NMDAR1反义寡核苷酸可缩小梗死体积,具有脑保护作用。 Objective To evaluate the therapeutic effects of antisense oligodeoxynuclcotides （ASODN） to NMDA receptor 1 on brain injury in experimental reversible middle cerebral artery occlusion （MCAO）. Methods Male Wistar rats were divided randomly into 3 groups：①lschemic-reperfusion group （n = 30） ： 2 hours of transient middle cerebral artery occlusion （MCAO） was induced;②Control group （n =30） ： 10μl PBS was injected into the lateral cerebral ventricle after MCAO;③ASODN group （n =30） ： 10 μl ASODN was injected into the lateral cerebral ventricle after MCAO. All the rats were given neurological evaluation before being sacrificed. The NMDAR1 was assayed by immunohistochemistry and the pathological changes were observed through microscopy, the infarct volume was measured with rITC staining. Results The neurological score in the ASODN group （ 1.4 ± 0. 5） was significantly lower than that of either in the ischemic-reperfusion group （2.4±0.6） or in the control group （2.5 ±0.4）. The protein levels of NMDAR1 were significantly different between ASODN group （36 ± 10） and the ischemic-reperfusion group （46 ±20） or the control group （50 ± 16）. The average infarct volumes of the ischemic-reperfusion group, control group and ASODN groupwere （42±3）%, （43±5）% and （28±4）% respectively. Condusion NMDAR1ASODN may decrease the infarct volume after transient MCAO and play a brain protective role against ischemic injury.
作者 张隽 丰宏林 姜海智 盛莉 孙威
机构地区 哈尔滨医科大学附属第四临床医学院神经内科 哈尔滨医科大学附属第一临床医学院神经内科 哈尔滨医科大学附属第一临床医学院风湿免疫科 哈尔滨医科大学附属第二临床医学院神经内科
出处 《中国脑血管病杂志》 CAS 2006年第5期228-231,共4页 Chinese Journal of Cerebrovascular Diseases
基金 黑龙江省攻关基金资助项目(GC03C6081) 黑龙江省普通高等学校骨干教师创新能力资助项目(2001)
关键词 脑缺血 再灌注损伤 寡核苷酸类 反义 大鼠 Cerebral ischemia Reperfusion injury N-methyl-D-aspartate receptor 1 Antisense oligodcoxynucleotide
分类号 R743 [医药卫生—神经病学与精神病学]
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参考文献9

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共引文献99

同被引文献54

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中国脑血管病杂志
2006年 第5期

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