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目的研究复方丹参滴丸(CDDP)与卡马西平(CBZ)合用对CBZ在正常和难治性癫痫(RE)大鼠脑内分布的影响。方法将Wistar雄性大鼠随机分为正常大鼠及造模大鼠;正常大鼠分为CBZ对照组及CDDP+CBZ组,造模大鼠分为CBZ模型组、CDDP+CBZ组及维拉帕米+CBZ组,造模大鼠采用脑立体定位技术向大鼠海马体内微量注射红藻氨酸建立RE模型,待模型成功点燃后,正常大鼠及造模大鼠中CDDP+CBZ组均给予CDDP(85 mg/kg),造模大鼠中维拉帕米+CBZ组给予维拉帕米(20 mg/kg),在连续ig给药10 d后各组ig给予CBZ(100 mg/kg)。在不同时间点采集大鼠脑组织样品,通过HPLC-MS/MS法测定CBZ脑药浓度。结果单用CBZ,正常大鼠脑内CBZ浓度明显高于RE模型大鼠;连续给予CDDP 10 d后,与单独给予CBZ相比,正常大鼠及RE模型大鼠所取的脑组织中CBZ浓度均有明显升高。在RE模型大鼠中,CDDP对CBZ脑药浓度的改变与经典的P-糖蛋白(P-gp)抑制剂维拉帕米对CBZ脑药浓度的改变趋势基本一致。结论 CDDP可提高正常及RE模型大鼠血脑屏障(BBB)对CBZ的通透性,增加CBZ在脑内的分布。
Objective To study the effect of combined use of CDDP and CBZ on CBZ distribution in normal and refractory epileptic rats. Methods Wistar male rats were randomly divided into normal rats and model rats. Normal rats were divided into CBZ control group and CDDP + CBZ group. The model rats were divided into CBZ model group, CDDP + CBZ group and verapamil CB + group and CB + + CBZ group. The rats were injected with kainic acid into the rat hippocampus to establish RE model by stereotaxic technique. After the model was successfully lit, the CDDP + CBZ group in normal rats and model rats were given Verapamil (20 mg / kg) was given to verapamil + CBZ group in the model group at a dose of 100 mg / kg (CDDP) ). Rat brain samples were collected at different time points and the concentration of CBZ brain drug was determined by HPLC-MS / MS. Results CBZ concentrations in brain of normal rats were significantly higher than that of RE model rats in CBZ group. Compared with CBZ group, CBZ concentrations in normal rats and RE model rats were significantly decreased Significantly increased. In RE model rats, the change of CBDP concentration in cerebral cortex was consistent with that of verapamil, a classic P-glycoprotein (P-gp) inhibitor, on CB concentration. Conclusion CDDP can improve CBZ permeability of BBB in normal and RE model rats and increase the distribution of CBZ in the brain.