Multidrug Resistance P-glycoprotein Overexpression Induced By Coriaria Lactone In Astrocytes Cultured From Rat Brains.

Objective: The aim of this study was to explore the possible pharmacoresistant mechanism by developing a kind of model of astrocytes cultured from rat brains induced by Coriaria lactone (CL).Method: Astrocyte cell cultures from postnatal Sprague-Dawley rats (within 24 hours of birth) were established. Different concentrations of CL(1ul, 3ul, 9ul, 15ul) were added to the cultures for 7, 14,21 or 28 days. The expression of P-glycoprotein (Pgp), the protein product of MDR1, was investigated with immunocytochemistry. Detect three indexes: Aera, MOD, IOD by using image analysis system.Result: In contrast with the control group,there was significant diference to 21-day group and 28-day group in upregulation of Pgp (P<0. 01) , but no difference to 7-day group and 14-day group(P>0. 05). Upregulation of Pgp had significant diference between 21-day group and 28-day group (P<0. 01) . Within the 21-day group and 28-day group , upregulation of Pgp was no dose-dependent manner (P>0. 05) .Upregulation of Pgp was detected when using any concentrations of CL on day 21,28 (P<0.01). On the day21,28, upregulation of Pgp was no dose-dependent manner (p>0.05) .Conclusion: 1, From day 14 to 28, CL induced the overexpression of Pgp in astrocytes in a time-dependent manner.As time went by, upregulation of Pgp was higher.2, Within the 21-day group and 28-day group , upregulation of Pgp was no dose-dependent manner.3, The study provided a ideal astocyte model of pharmacoresistant epilepsy induced by CL. The increased expressions of P-gp might involve in induction of the pharmacoresistance.