新生大鼠反复惊厥对脑内γ-氨基丁酸A受体α1和β2亚单位表达的长期影响  

Long-term effects of recurrent seizures in neonate period on γ-aminobutyric acid A receptor α1 and β2 subunits expression in adult brain:experiment with rats

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

机构地区：[1]中南大学湘雅二医院儿科,长沙410011

出　　处：《中华医学杂志》2007年第4期275-278,共4页National Medical Journal of China

基　　金：国家自然科学基金青年科学基金(30400483)

摘　　要：目的研究新生期大鼠反复惊厥对脑内γ-氨基丁酸(GABA)A 受体(GABAAR)α1和β2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。方法生后7 d 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30 min,连续6 d;对照组同样操作但不吸入三氟乙醚。两组大鼠于生后61～65 d 行 Morris 水迷宫实验,于生后75 d 时通过腹腔注射戊四唑测定大鼠的惊厥阈。随即处死大鼠,分别采用免疫组化和逆转录 PCR 方法观察大鼠大脑皮层及海马 GABAAR α1和β2亚单位表达的变化。结果生后64 d 的寻找平台时间(82 424ms±35 622 ms)明显长于对照组(40 712 ms±29 467 ms,P=0.001)。在生后65 d,惊厥组大鼠120 s内穿越目标次数(1.2次±0.9次)明显少于对照组(3.1次±1.3次,P<0.01)。惊厥组大鼠注射PTZ 后发生惊厥的潜伏期(1487 s±662 s)与对照组(1841 s±648 s)差异无统计学意义(P=0.133)。惊厥组大鼠 GABAAR α1亚单位免疫化学累积吸光度在顶叶及海马 CA1、CA2和 CA4区明显低于对照组(均 P<0.05);惊厥组大鼠 GABAAR β2亚单位免疫化学累积光密度在丘脑区和海马 CA1～4区明显低于对照组(均 P<0.05)。惊厥组大鼠海马α1和β2亚单位 mRNA 的表达明显少于对照组(均P<0.05)。结论新生大鼠反复惊厥可造成脑内 GABAAR α1和β2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 recurrent seizures in neonate period on the expression of T-aminobutyric acid A receptor （GABAAR） α1 and β2 subunits in brain and spatial memory and seizure susceptibility in adult period. Methods Thirty-two 7-day-old SD rats were randomly divided into 2 equal groups： seizure group, inhaling flurothyl to induce seizure daily for 6 days, and control group. On days 61-65 after birth Morris water maze test was used to record the escape latency. On day 75 after birth pentylenetetrazol （PTZ） was injected intraperitoneally to induce seizure so as to record the latency. Then the rats were killed to take their brains, 8 in each group used to undergo immunohistochemistry to examine the protein expression of the GABAAR α1 and β2 subunits, and the other 8 in each group used to examine the mRNA expression of the GABAAR α1 and β2 subunits in the brains using RT-PCR. Results On day 64 the escape latency of the seizure group was 82 424 ms ± 35 622 ms, significantly longer than that of the control group （40 712 ms ± 29 468 ms, P = 0. 001 ）. On day 75 the frequency of crossing target within 120 s in the water maze of the seizure group was 1.2 times ± 0.9 times, significantly less than that of the control group （ 3.1 times ＋ 1.3 times, P 〈 0.01 ）. The seizure latency after the PTZ injection of the seizure group was （ 1487 ± 662 ） s, not significantly different from that of the control group （1841 s±648 s, P=0. 133）. In comparison with the control group the accumulated optical density （AOD） of GABAAR α1 snhunit protein immunoactivity in the parietal cortex, and hippocampal CA1-2 and CA4 regions of the seizure group decreased significantly （ all P 〈 0.05 ） , and was not significantly different in the frontal cortex, dentate gyrus, and hippocampal CA3 region （ all P 〉 0.05 ）. In comparison with the control group the accumulated optical density （AOD） of GABAAR β2 snhunit protein immunoactivity in the thalamus, and hippocamp

关 键 词：惊厥 动物 新生 受体 GABA-A 

分 类 号：R720.597[医药卫生—急诊医学]