Antisense GAD67 ODN对戊四氮所致慢性癫痫大鼠作用的研究

摘要

目的　探讨谷氨酸脱羧酶(GAD)的抗癫痫作用。方法　采用戊四氮制备大鼠慢性癫痫模型，利用反义寡脱氧核苷酸技术，通过选择性地抑制海马GAD基因的表达来观察其对慢性癫痫大鼠行为、发作阈值及脑电图的影响；同时，采用高效液相色谱法检测其对海马组织内γ-氨基丁酸（GABA）含量的影响。结果　给予Antisense GAD67 ODN处理后，GAD67 mRNA表达下降、GABA浓度下降、痫性发作潜伏期缩短、发作程度加重及脑电图痫波频率增加。结论　从反面进一步说明GAD基因可能是抗痫基因，为GAD基因治疗癫痫提供实验依据。%Objective To investigate the effects of antisense glutamic acid decarboxylase (GAD67) oligodeoxynucleo- tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetrazol (PTZ). Methods A model of chronic epilepsy in rats was established by PTZ. The inhibition of GAD67 mRNA expression in hippocampus was selectively induced by antisense oligodeoxynucleotide of GAD67. The effect of antisense GAD67 ODN on behavior, seizure threshold and EEG recording of kindled rats was examined. Results Antisense GAD67 ODN could inhibit the expression of GAD67 mRNA and the concentration of GABA. It also could significantly shorten the latencies of seizure and increase the level of seizure and the frequency of epileptiform discharges. Conclusion The gene of GAD67 may be an anti-seizure gene, which might inhibit epileptiform discharge. The treatment of epilepsy by GAD67 gene will have a bright future.