Objective: To explore the antiepileptic effect of Dingxianwan in rats with refractory epilepsy and investigate its possible molecular mechanism. Method: The 90 healthy male Wistar rats were randomly divided into two groups:normal control group (n=10) and refractory epilepsy model group (n=80). Then

64 successful modeling rats were randomly divided into model group

Dingxianwan group

carbamazepine group and integrated Chinese and western medicine group

with 16 rats in each group. The rats in Dingxianwan group were ig administered with Dingxianwan suspension 1.5 g·kg-1·d-1; rats in carbamazepine group were ig administered with carbamazepine solution 30 mg·kg-1·d-1; rats in integrated Chinese and western medicine group were ig administered with Dingxianwan suspension 1.5 g·kg-1·d-1 +carbamazepine solution 30 mg·kg-1·d-1

while rats in normal control group and model group were ig administered with normal saline 15 mL·kg-1·d-1. Administration lasted for one month. Then the antiepileptic effects of Dingxianwan were evaluated by behavior and electroencephalogram (EEG). The effects of Dingxianwan on carbamazepine concentration in rat brains were evaluated by high performance liquid chromatography (HPLC) method. The multi-drug resistance gene 1 (MDR1) and P-glycoprotein (P-gp) protein and mRNA expression levels in rat brains were detected by immunohistochemistry

Western blot and real time polymerase chain reation (Real-time PCR) techniques. Result: In normal control group

there was no epileptic attack and only a small amount of MDR1

P-gp expressed in rats brain. As compared with normal control group

the epileptic seizure grade was higher (P<0.05); the duration was longer (P<0.05) and MDR1

P-gp expression levels were higher (P<0.05) in the cortex and hippocampus of model group rats. As compared with model group

the grade and duration of epileptic seizures in experimental groups were lower (P<0.05)

and the expression levels of MDR1

P-gp in brains were significantly lower (P<0.05). As compared with Dingxianwan group

the seizure grade was lower (P<0.05); the duration was shorter (P<0.05) and the expression levels of MDR1

P-gp were lower in the integrated Chinese and western medicine group (P<0.05). As compared with carbamazepine group

the expression levels of MDR1

P-gp in brains were lower in Dingxianwan group and integrated Chinese and western medicine group; the seizure grade was lower (P<0.05) and duration was shorter (P<0.05) while the concentration of carbamazepine in the brain of rats was higher in rats of integrated Chinese and western medicine group (P<0.05). Conclusion: Dingxianwan has certain antiepileptic effect on refractory epilepsy and can reverse carbamazepine resistance

showing synergistic effect. The reversal of drug resistance may be related to the blocking of MDR1

P-gp expression in rat brains.