Effect of Oxcarbazepine on multidrug resistance associated protein 1 expression in hippocampus of kainic acid-induced seizure in rats during development period rats / 中华实用儿科临床杂志

ABSTRACT

Objective To observe the expressions of multidrug resistance-associated protein (MRP) 1 in the hippocampus of the rat models with chronic epilepsy,and to explore whether antiepileptic drug oxcarbazepine(OXC) affects the expression of MRP1.Methods One hundred rats of 14 days old were randomly divided into model group(n =52) and the control group(n =48).The model group received intraperitoneal injection of kainic acid(KA) 1 mg/kg (0.5 g/L) to induce seizures,and the control group rats were injected the same dose of 9 g/L chloride.According to Lado standard classification of seizures,the young rats whose seizure degree was beyond 5 and became status epilepticus after intraperitoneal injection used as successful seizure models if they caught the spontaneous seizures after 2 weeks.When spontaneous seizures were developed,48 surviving KA rats were divided into KA group and KA + OXC group.Rats in the control group were divided into NS group and NS + OXC group.After spontaneous recurrent seizures,the treatment groups began to take drugs.Each group started to be sacrificed from the beginning of drug perfusion at different times and they were divided into the 4th week group,the 6th week group and the 8th week group.The expression of MRP1 in hippocampus(CA3 area) was detected by immunohistochemistry methods.Results 1.Epileptic performance:all rats injected with NS had no epileptic performance.In the chronic epilepsy,Ⅰ-Ⅴ Racine grade of spontaneous recurrent seizures were found in all rats with KA.The rats in KA group had higher epilepsy seizure frequency than those in KA + OXC group (P ＜ 0.05).2.The rats in NS group and NS + OXC group had fewer MRP1 positive cells,and there was no significant difference at all time points between NS group and NS + OXC group (P ＞ 0.05).The trend of expression in KA group and KA + OXC group gradually increased.The MRP1 positive cells in KA + OXC group compared with those in the KA group was significantly different in the 8th week(P ＜0.05),while there was no significant difference in the 4th week and the 6th week(all P ＞0.05).And there was a significant difference in the positive cells in KA group compared with those of KA group(P ＜0.05).The expression of MRP1 positive cells in KA + OXC group increased significantly compared with those in NA + OXC group(all P ＜ 0.05).Conclusions MRP1 plays an important role in resistance mechanisms of refractory epilepsy,while the expression of MRP1 can be induced by using OXC in a long term.