Influence of scorpion alcoholic extraction on mdr1 mRNA and P-gp expression in brain of phenytoin-resistant convulsive rats / 中国中药杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study the anticonvulsive action of scorpion alcoholic extraction (SAE) on phenytoin-resistant convulsive rats made by direct cortical electrical stimulation in order to investigate the mechanism of antagonizing drug-resistance of SAE.</p><p><b>METHOD</b>Using the method of implanting microelectrodes in the cortical motor area of the brains of rats where the brain tissue was stimulated frequently by electricity through microelectrodes until igniting and then PHT (0.154 g x kg(-1) x d(-1)) ig for 7 days, We established phenytoin-resistant convulsive rat model. Total 6 groups were set up in the experiment Normal control group, convulsion model control group (CMCG), phenytoin-resistant convulsion control group (PRCG), verapamil positive control group (VPCG, 0.0385 g x kg(-1)), scorpion alcohol extraction (SAE1, 6.5 g x kg(-1)) and scorpion alcohol extraction (SAE2, 13.0 g x kg(-1)). After ig both doses of SAE (6.5, 13.0 g x kg(-1)), the effects of SAE on the changes of convulsion threshold of phenytoin-resistant convulsive rats were observed. The method of RT-polymerase chain reaction (RT-PCR) was used to detect the changes of mdrl gene expression and the method of immunohistochemistry (SABC) was adopted to determine the changes of P-gp expression.</p><p><b>RESULT</b>Both doses of SAE and verapamil (Ver) ig all raised the convulsant threshold of phenytoin-resistant rats (480.38 +/- 18.48) microA, there were statistical differences (P < 0.05) compared to themselves before drugs-treated. PHT was administrated, and mdrl mRNA and P-gp expression in PRCG was much higher than that in CMCG, with significantly statistical difference (P < 0.01); ig both doses of SAE and Ver all decreased mdrl mRNA and P-gp expression compared to PRCG respectively (P < 0.01).</p><p><b>CONCLUSION</b>SAE and Ver ig all produce antagonizing action on phenytoin-resistant convulsive rat model. The machanism is related with inhabiting the mdrl mRNA expression and further decreasing the product P-gp.</p>