复方丹参滴丸对卡马西平在正常大鼠及难治性癫痫大鼠脑内分布的影响

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。

Effect of Compound Danshen Dripping Pills on distribution of carbamazepine in brain of normal and refractory epilepsy rats

Objective To investigate the effect of Compound Danshen (Salvia miltiorrhiza) Dripping Pills (CDDP) on the distribution of carbamazepine (CBZ) in the brain of normal and refractory epilepsy rats. Methods Wistar male rats were divided into normal and model rats. Normal rats were divided into control group and CDDP group. Model rats were divided into control group, CDDP group and verapamil group. The animal model of refractory epilepsy was induced by intrahippocampal injection of kainic acid. After the success of modeling, CDDP group was given CDDP (85 mg/kg), verapamil group was given verapamil (20 mg/kg) for 10 d, then each group was given CBZ (100 mg/kg) respectively. Brain tissue samples were collected at different time points. After the samples were pretreated, the concentration of CBZ in the brain tissue was detected by HPLC-MS/MS. Results When using carbamazepine alone, the concentration of CBZ in normal rats was obviously higher than epileptic rats. Compared with using carbamazepine alone, CDDP could significantly increase the concentration of CBZ in normal and epileptic rats. For the epileptic rats, the enhancing effect of CDDP to the cerebral distribution of CBZ was similar to that of P-glycoprotein inhibitor verapamil. Conclusion CDDP could enhance the permeability of blood-brain barrier to CBZ and increase the cerebral distribution of CBZ in normal and epileptic rats.