新生大鼠反复惊厥对脑内γ-氨基丁酸A受体α1和γ2亚单位表达的长期影响  

Long-term effects of neonatal recurrent seizures on γ-aminobutyric acid A receptor α1 and γ2 subunit expressions in the rat brain

作　　者：薄涛[1] 陈勇[2] 毛定安[1] 李艳芳[1] 朱晓华[1] 

机构地区：[1]中南大学湘雅二医院儿科,长沙410011 [2]江西省儿童医院神经内科

出　　处：《北京大学学报（医学版）》2006年第6期628-633,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金青年科学基金资助项目(30400483)~~

摘　　要：目的：研究新生期反复惊厥对大鼠脑内γ-氨基丁酸（γ-aminobutyric acid，GABA）A受体α1和γ2亚单位表达的长期影响，及成年期记忆功能和惊厥阈的长期改变。方法：将生后7天（postnatal 7d，P7）的SD大鼠随机分成两组，每组16只，惊厥组每日吸入三氟乙醚诱导惊厥发作1次，每次持续30min，连续6d；对照组同样操作但不吸入三氟乙醚。两组大鼠于出生后第61～65天（P61～P65）行Morris水迷宫实验，于P75时给予大鼠腹腔注射戊四唑测定大鼠的惊厥阈。随即处死大鼠，分别采用免疫组化方法和RT-PCR方法观察大鼠大脑皮层及海马GABAA受体（GABAAR）α1和γ2亚单位表达的变化。结果：惊厥组大鼠在P64的寻找水下平台时间[（82424±35622）ms]较对照组[（40712±29467）ms]明显延长（P=0．001）。在P65，惊厥组大鼠120s内穿越原平台位置次数[（1．2±0．9）次]较对照组[（3．1±1．3）次]明显减少（P〈0．001）。惊厥组大鼠注射戊四唑后发生惊厥的潜伏期[（1487±662）s]与对照组[（1841±648）s]比较差异无统计学意义（P=0．137）。惊厥组大鼠GABAARα1亚单位免疫化学累积光密度在顶叶及海马CA1、CA2和CA4区较对照组明显降低（P〈0．05）；惊厥组大鼠GABA。R12亚单位免疫化学累积光密度在额叶和海马CA4区较对照组明显降低（P〈0．05）。惊厥组大鼠大脑皮层GABAARγ2亚单位和海马区α1亚单位mRNA的表达较对照组明显减少（P〈0．05）。结论：新生大鼠反复惊厥可造成脑内GABA。Rα1和γ2亚单位表达的长期改变，这种改变可能与新生期反复惊厥导致的成年期记忆障碍相关。Objective： To investigate the long-term effects of flurothyl-induced neonatal recurrent seizures on GABA A receptor （ GABAAR） α1 and γ2 subunit expressions in adult rat brain, and discuss the relationship between these alterations of GABAAR subunits in mature brain and the changes of spatial memory and seizure susceptibility in adult rats. Methods： Thirty-two of 7-day-old （P7） Sprague-Dawley rats Were divided randomly into two groups： the control group and the seizure group. Seizures were induced by inhalant flurothyl daily for six consecutive days. Rats were tested for spatial memory by using the Morris water maze task from postnatal 61 d（ P61 ） to P65. Seizure threshold was examined by intraperitoneal injection of pentylenetetrazol, and then the brains were sampled on P75. The expressions of GABAAR etl and γ2 subunits mRNA and protein in cerebral cortex and hippocampus were detected by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry method. Results： On P64, the escape latencies in water maze for the rats in the seizure group were significantly longer than those of the control rats [ （ 82 424 ± 35 622） ms vs （40 712 ± 29 468） ms, P = 0.001 ]. On P65, the frequency of crossing target within 120 s in water maze for the rats in the seizure group were significantly less than those of the control rats [ （ 1.2 ±0.9） vs （3.1 ± 1.3）, P 〈0.001 ]. There was no difference in seizure threshold between the two groups on P75 [ （ 1 487 ± 662） s vs （ 1 841± 648 ） s, P = 0. 137 ]. Compared to the control rats, the accumulated optical density （AOD） of GABAAR α1 subunit immunoreactivity in seizure rats decreased significantly in the parietal cortex, CA1-2 and CA4 region （P 〈0.05）.The AOD of α1 subunit protein immunoreactivity in the frontal cortex, CA3 and dentate gyrus （DG） were of no significant difference between the two groups on P75 （ P 〉 0.05 ）. There were also no differences in the AOD of γ2 subunit protein i

关 键 词：惊厥 受体 GABA-A 动物 新生 大鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学]