卡马西平对青霉素点燃癫痫大鼠脑内GABA_B受体蛋白表达的影响

目的研究两种剂量卡马西平(CBZ)对青霉素慢性点燃大鼠的抗癫痫作用及对癫痫大鼠脑内GABAB受体蛋白表达的影响,从蛋白水平探讨CBZ抗癫痫作用的新机制。方法采用腹腔注射青霉素(PNC,3×106U·kg-1·d-1×13d)慢性点燃大鼠癫痫模型,两种剂量CBZ(50和100mg/kg体质量)灌胃给药,以痫性发作潜伏期和Racine癫痫行为分级标准为判定指标,观察CBZ的抗癫痫作用。用免疫组织化学SABC法测定大鼠脑内GABAB受体蛋白表达,分析CBZ对GABAB受体蛋白表达的影响。结果两种剂量CBZ灌胃给药后,均可使青霉素慢性点燃大鼠痫性发作的潜伏期延长,与模型对照组相比差异有统计学意义(P<0.01),同时使癫痫大鼠的发作程度均较模型对照组减轻。青霉素慢性点燃大鼠脑内GABAB受体蛋白表达量较正常组降低,两者比较差异有统计学意义(P<0.05)。CBZ1组、CBZ2组脑内GABAB受体蛋白表达量分别与正常对照组和模型对照组比较,均显示增高,且差异有统计学意义(P<0.05)。结论两种剂量CBZ可延长青霉素慢性点燃大鼠痫性发作的潜伏期,减轻发作程度,具有明显的抗癫痫作用。青霉素慢性点燃大鼠癫痫发作与降低脑内GABAB受体蛋白表达有关,而CBZ抗癫痫作用机制与增加大鼠脑内GABAB受体蛋白表达有关。

The influences of carbamazepline on GABAB-R protein expression in brain of PNC-kindled convulsant rats

Objective To investigate the antiepileptic action and influence of two dosages of carbamazepine （CBZ）on GABAB receptor protein expression in chronic penicillin （PNC） kindled convulsant rats,and to explore its new anticonvulsive mechanism from protein aspect. Methods The model of chronic PNC-kindled convulsant rats （3×10^6 U·kg^-1·d^-1×13 d,ip） was used to investigate the effects of CBZ （50 mg·kg^-1-100 mg·kg^-1,ig）on the latency of seizure and the changes of convulsant behaviors. Strept Actividin-Biotin Complex （SABC） was adopted to determine the impact of CBZ on protein expression of cerebral GABAB receptor and the anticonvulsive mechanism of CBZ was analyzed. Results Both doses of CBZ prolonged seizure latency with statistical differences compared with findings from model group （P〈0.01）. Furthermore, CBZ decreased the severity of seizure. Compared with that of model group and normal group respectively, the quantity of GABAs receptor protein expression in rats treated with doses of CBZ increased （P〈0.05）. Conclusion Both doses of CBZ produced anticonvulsive action in models of PNC-kindled convulsant rats. Epileptic seizure in PNC-kindled rats may be related to decreased GABAB receptor protein expression,and the anticonvulsive mechanism of CBZ might be related to the increase of protein expression of GABAB receptor.