目的 探讨天然冰片对甲氨蝶呤（MTX）透过血肿瘤屏障的影响。方法 采用立体定向技术，以C6胶质瘤细胞建立C6脑胶质瘤大鼠模型，14 d后，将模型大鼠随机分为对照组（0.5 %羧甲基纤维素钠），冰片高、低剂量组（140，35 mg•kg-1）。灌胃给药1 h后，3组大鼠均尾静脉注射MTX 20 mg•kg-1，于注射后不同时间点采集血样及脑组织，高效液相色谱法测定血浆与脑组织中MTX的浓度，并计算主要药动学参数。结果 与对照组比较，冰片高、低剂量组的血浆中MTX AUC0-t，AUC0-∞均显著降低（P＜0.01）；冰片高剂量组脑组织中MTX AUC0-t，AUC0-∞显著升高（P＜0.05），冰片低剂量组脑组织中MTX AUC0-t，AUC0-∞亦有升高趋势，但差异无统计学意义（P \> 0.05）。结论 天然冰片可增加MTX在C6脑胶质瘤模型大鼠脑组织中的分布，提高其在脑组织中的生物利用度。

Objective To establish a C6/SD glioma model and to explore the effects of natural borneol on the penetration of methotrexate（MTX） across blood tumor barrier. Methods Horseley-Clarke technique was used for the establishment of C6/SD glioma model. Fourteen days after the modeling，the model rats were randomly divided into control group（0.5 % sodium carboxymethyl cellulose），low-dose borneol group（35 mg•kg-1 borneol） and high-dose borneol group（140 mg•kg-1）. One hour after intragastrical administration，MTX（20 mg•kg-1） were injected into the rats of the three groups through caudal vein. Plasma and brain tissue samples were collected at corresponding time after intravenous injection. The concentrations of MTX in the plasma and brain were determined by high performance liquid chromatography，and the main parameters were determined by software PK-solution 2.0. Results Plasma AUC0-t and AUC0-∞ of MTX in the high- and low-dose borneol groups were obvious lower than the control group（P＜0.01）. AUC0-t and AUC0-∞ of MTX in the brain of high- and low-dose borneol groups were higher than control group，and the difference between high-dose group and control group was significant（P＜0.01），whereas between low-dose group and control group was insignificant（P \> 0.05）. Conclusion Natural borneol can increase the distribution of MTX in C6/SD glioma model，and improve the bioavailability of MTX in the brain.

R285.5

国家自然科学基金（81173379）。