P-糖蛋白限制经血脑屏障的尼莫地平转运(英文)

目的:研究P-糖蛋白(P-gp)是否限制尼莫地平(NMD)从血液循环进入脑内。方法:当原代培养的鼠脑微血管内皮细胞(BCEC)长至互相连接成片时,加入含有NMD 10mg/L的Hanks’液37℃温孵,记录细胞摄取NMD的时间过程,将含有NMD和各种不同受试药物的Hanks’液分别加入到不同培养孔中,检测90min时细胞对NMD的摄取量,在细胞摄取NMD 90min后,分别加入红霉素,克拉霉素和环孢素A以检测P-糖蛋白抑制剂对原代培养的脑微血管内皮细胞外排NMD的影响。结果:细胞对NMD的摄取呈时间依赖性,P-gp抑制剂或代谢抑制剂的加入会增加稳态时NMD在细胞内的浓度,P-gp抑制剂的加入也使NMD的外排受到了抑制。结论:P-gp限制NMD进入脑内,P-gp抑制剂的加入可增加NMD的进入。

P-glycoprotein restricted transport of nimodipine across blood-brain barrier

AIM: To examine whether the transport of nimodipine (NMD) from the circulating blood into the brain is restricted by P-glycoprotein (P-gp) in rat brain capillary endothelial cells (BCEC). METHODS: When cells reached confluence, a time course of NMD uptake was recorded by incubation with a medium containing NMD 10 mg/L at 37 degrees C. Effects of various agents in the steady-state uptake of NMD were tested by co-administration with NMD and each compound to cells at 37 degrees C for 90 min. The uptake of NMD was measured for 90 min. Effects of P-gp inhibitors on the efflux of NMD from primary cultured BCEC were studied by administration of erythromycin, clarithromycin, cyclosporin A (CsA), and Hanks' solution after the accumulation of NMD by BCEC at 37 degrees C for 90 min. RESULTS: The uptake of NMD by primary cultured rat BCEC was time-dependent, and the steady-state uptake of NMD was increased in the presence of several substrates of P-gp in BCEC. The steady-state uptake was also significantly increased (P<0.01) when cellular ATP was depleted by treatment with sodium azide. Furthermore, efflux of NMD from BCEC was inhibited by erythromycin,clarithromycin, and CsA. CONCLUSION: The permeability of NMD into the brain is restricted by P-gp and increased by co-administration with P-gp inhibitors.