The Influences Of Carbamazepine On GABA_A Receptor MRNA And GABA_B-R Protein Expression In Brain Of Epilepsy Rats

Objective To investigate the antiepileptic action and influence of both doses of carbamazepine(CBZ) on GABA_A receptor mRNA expression and GABA_B receptor protein expression in penicillin(PNC) chronicly kindling rat,and explore its new antiepileptic mechanism from gene and protein levels.Methods Using the model of epileptic rats chronicly kindled by penicillin(3×10⁶U·kg^-1·d^-1·13d,ip)investigated the effect of CBZ(50mg·kg^-1,100mg·kg^-1,ig)on the latency of seizure and the changes of epileptic behaviors.Reverse transcriptase-polymerase chain reaction(RT-PCR)was adopted to determine the impact of CBZ on mRNA expression of cerebral GABA_A receptor and Strept Actividin-Biotin Complex(SABC) was adopted to determine the Values of GABA_B receptor protein expression,which were used to analyze the influence of CBZ on GABA_A receptor mRNA expression and GABA_B receptor protein expression.Results In model group,after ip administration penicillin for 13d,7 rats had severe seizure and 1 rat appeared mild seizure,and the latency of seizure was 15.7±2.39min;In CBZ1(CBZ 50mg) group,1 rat had severe seizure and 7 rats appeared mild seizure,and the latency of seizure was 22.8±3.31min;In CBZ2(CBZ 100mg) group,all 8 rats appeared mild seizure and no one appeared severe seizure,and the latency of seizure was 32.2±4.07min.Both doses of CBZ could prolong seizure latency and there were statistical difference compared with model group(P＜0.01).Furthermore,CBZ weakened seizure degree in rats with epilepsy.Determine results of PCR:Compared with normal rats,GABAA receptor mRNA expression in PNC chronicly kindling rat cerebrum decreased,there was significant statistical difference (P＜0.01).In pre-intervention groups of both doses of CBZ,compared with normal group and model group respectively,the changes of quantity of GABA_A receptor mRNA expression had not statistical difference(P＞0.05).Determine results of SABC:The quantity of the GABA_B receptor protein expression in PNC chronicly kindling rat cerebrum was 0.226±0.01,and less than that of the normal group(0.265±0.01),with statistical difference(P＜0.05).In CBZ1 and CBZ2 groups,the quantity of the GABA_B receptor protein expression were 0.297±0.03 and 0.308±0.04 respectively,and both of them were more than that of the normal group and model group respectively,there were statistical difference between them(P＜0.05).Conclusions(1).Both doses of CBZ could prolong seizure latency and weakened seizure degree,so that produced antiepileptic action in the model of epileptic rats chonically kindled by PNC. (2)Epileptic seizure of PNC chronicly kindling rat is related to decrease of GABA_A receptor mRNA expression,but antiepileptic mechanism of CBZ might not be related to the changes of GABA_A receptor gene expression.(3)Epileptic seizure of PNC chronicly kindling rat is related to decrease of GABA_B receptor protein expression,and antiepileptic mechanism of CBZ might be related to the increase of protein expression of GABA_B receptor.