P-糖蛋白对大鼠海马细胞外液卡马西平浓度的调节作用研究

Study the Function of P-glycoprotein in Modulating the Extracellular Levels of Carbamazepine in Hippocampus of Chronic Epileptic Rats

目的观察P-糖蛋白对海马细胞外液卡马西平浓度的调节,评估维拉帕米的干预作用。方法采用微透析技术,按实验需要将实验动物分为正常、慢性癫痫(PTZ)组及维拉帕米干预组,每组10只大鼠,分别测定海马细胞外液、血清卡马西平浓度,并计算细胞外液/血清比值。结果慢性癫痫大鼠海马细胞外液卡马西平浓度明显低于正常大鼠,而两组血浓度相差不大;通过探针局部灌注Verapamil可提高CBZ在脑中的浓度,使得其与血中的浓度比值也相应提高。结论P-gp能调节脑细胞外液卡与西平浓度;予P-gp抑制剂维拉帕米,可提高细胞外液药物浓度。

Objective To evaluate the regulatory function of P-glycoprotein at extra cellular level of carbamazepine in hippocamopus and the effect of Verapamile. Methods Rats were classified into three groups as following： normal group, PTZ group and Verapamile group. The extra cellular level and serum level of carbamazepime in hippocampus （ECA） of each rat was measured and their ratio was calculated. Results The extra cellular level of carbamazepine in hippocampus of chronic epileptic rats was lower than that in normal rats. The level of carbamazepine was increased with the treatment of Verapamile via a microdialysis probe. The dialysate-plasma ratio was increased slgnificanthy subsequently. Conlusion Pgp can modulate extra cellular level of carbamazopine; with the admin stration of P-gp inhibitor, the extra cellular level of carbamazepine was increased.