N-甲基-D-天冬氨酸受体在缺氧缺血性脑损伤新生大鼠脑海马中的远期表达  

Long-term expression of N-methyl-D-aspartate receptor in the hippocampus of neonatal rats with hypoxia-ischemic brain damage

作　　者：刘晓蓉[1] 赵聪敏[1] 于若谷[1] 

机构地区：[1]解放军第三军医大学新桥医院儿科,重庆市400037

出　　处：《中国组织工程研究与临床康复》2007年第16期3089-3092,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：目的:观察新生大鼠缺氧缺血性脑损伤后,海马发育过程中N-甲基-D-天冬氨酸受体的远期表达变化。方法:实验于2006-03/06在解放军第三军医大学新桥医院中心实验室完成。选用新生7日龄SD大鼠72只,按随机数字表法分为缺氧缺血性脑损伤组和假手术组,每组36只。各组又分为生后15d(n=6)、22d(n=6)、29d(n=6)、36d(n=12)及43d(n=6)5个时相点。①参照Rice法通过结扎7日龄大鼠左侧颈总动脉,吸入氧气体积分数为0.08的氮氧混合气,制成缺氧缺血性脑损伤模型,出现自发或夹尾左旋则证明模型制作成功。假手术组仅切开颈部皮肤,暴露左侧颈总动脉。②应用免疫组织化学法检测缺氧缺血后不同时点两组大鼠脑海马CA1区N-甲基-D-天冬氨酸受体NR1亚单位的表达(n=6),测量平均灰度值,灰度值越低,蛋白表达越强;生后36d时相点大鼠(n=6)利用Morris水迷宫测定学习记忆能力;最后应用电镜观察生后36d大鼠海马突触结构。结果:72只大鼠,全部进入结果分析,无脱失。①生后22-43d缺氧缺血性脑损伤组大鼠(缺氧缺血后15-36d)脑海马CA1区NR1平均灰度值分别为167.69±6.48,174.57±4.81,179.30±5.92,176.50±5.93,均显著高于同日龄假手术组148.96±4.91,151.17±6.37,152.06±9.86,156.32±6.86(P均<0.01)。②Morris水迷宫实验中,缺氧缺血性脑损伤组大鼠逃避潜伏期显著长于假手术组(48.87±9.47)s,(11.97±2.20)s,(P<0.01);原平台象限游泳距离/总游泳距离的百分比显著低于假手术组(14.45±3.85)%,(62.20±8.74)%(P<0.01)。③生后36d(缺氧缺血后29d),透射电镜下缺氧缺血性脑损伤组大鼠患侧海马突触后膜致密物较假手术组明显减少。结论:新生大鼠缺氧缺血性脑损伤后期存在海马N-甲基-D-天冬氨酸受体的表达下调,可能对大鼠远期空间学习记忆产生一定影响。AIM： To observe the long-term expression of N-methyl-D-aspartate （NMDA） receptor during the hippocampal development of neonatal rats with hypoxic-ischemic brain damage. METHODS： The experiment was performed in the Central Laboratory of Xinqiao Hospital, Third Military Medical University of Chinese PLA from March to June 2006, Seventy-two postnatal day 7 SD rats ware randomly divided into hypoxia-ischemia group and sham operation group with 36 rats in each group, Then, the groups ware subdivided into five time-points as 15 days （n =6）, 22 days （n =6）, 29 days （n =6）, 36 days （n =12） and 43 days （n =6）.（1）Models of hypoxic-ischemic brain damage ware established by the Rice method as follows： The left carotid of the rats was ligated following the inhalation of nitrogen oxygen atmosphere containing 0,08 volume fraction oxygen, If the rats spontaneously or tail-clip left rotation, the models ware made successfully, The sham operation group was only given neck skin discission to expose the left carotid, （2）Immunohistochemistry method was used to detect the expression of NMDA receptor NR1 subunit in hippocampal CA1 region at different time points （n =6）, The average gray values were measured; the lower the values, the stronger the protein expression; Morris water maze and electron microscope ware used, respectively to test the learning and memory abilities and synaptic structure of the rats of postnatal day 36. RESULTS： Seventy-two rats were involved in the result analysis without any loss. （1）From postnatal day 22 to 43, the mean gray values of NR1 in hippocampal CA1 region of the hypoxia-ischemia group （15-36 days after hypoxia-ischemia）. ware （167.69±6.48）, （174.57±4.81）, （179.30±5.92）, （176.50±5.93）, which were higher than the sham operation group at the same time points （148.96±4.91）, （151.17±6.37）, （152.06±9.86）, （156.32±6.86）, P 〈 0.01. （2）In the Morris water maze test, the escape latency of the hypoxia-ischemia g

关 键 词：缺氧缺血 脑 受体 N-甲基-D-天冬氨酸/代谢 记忆 学习 

分 类 号：R743[医药卫生—神经病学与精神病学]