Rna Interference Suppression Of Mdr1 Expression Of The Rat Brain Astrocytes Induced By Coriaria Lactone

Objective Epilepsy is one of the most common neurological disorders. Despite advances in antiepileptic drug (AED) therapy, about one-third of patients with epilepsy are resistant to drug treatment . In medically refractory epilepsy, resistance mechanisms that involve drug transporters overexpessed in capillary endothelial cells and astrocytes of the blood - brain barrier (BBB) and the blood - cerebrospinal fluid (blood-CSF) barrier are among the most intensively interested in. P-gp is one important part of multi-drug resistance protein.The efflux pump P-gp can not only limit AEDes penetrating brain parenchyma but also reduce the amount of drug that reaches the epileptic neurons and its peritissues,which leads to poor clinical outcomes.The aim of this study was to transfect astrocytes expessing P-gp induced by Coriaria Lactone with the siRNA-hairpin expression vector-p-SIREN shuttle.The impact of the RNAi upon MDR1mRNA and P-gp expression as well as drug resistance reversal was assessed.Methods Astrocytes expessing P-gp induced by Coriaria Lactone were transfected with the siRNA-hairpin expression vector p-SIREN shuttle designed to target MDR1mRNA.The mRNA expression of MDR1 gene was evaluated by Real-time PCR,the P-gp was examined by immunocytochemistry and image analysis and the Rhodamine efflux was assessed by flow cytometer.Results We established the astocyte model expressing P-gp and successfully transfected it with the siRNA-hairpin expression vector-p-SIREN shuttle. The mRNA expression of MDR1 gene evaluated...