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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 investigate the effect of natural borneol on the transmembrane barrier of methotrexate (MTX). Methods C6 glioma rat model was established with C6 glioma cells by stereotactic technique. After 14 days, the model rats were randomly divided into control group (0.5% sodium carboxymethyl cellulose), high and low borneol Dose group (140, 35 mg · kg-1). One hour after intragastric administration, the rats in the three groups were injected MTX 20 mg · kg-1 through the tail vein, and blood samples and brain tissues were collected at different time points after injection. The concentrations of MTX in plasma and brain tissues were determined by high performance liquid chromatography , And calculate the main pharmacokinetic parameters. Results Compared with the control group, MTX AUC0-t and AUC0-∞ in plasma were significantly decreased (P <0.01), and the contents of MTX AUC0-t and AUC0-∞ in the high-dose borneol group were significantly increased (P <0.05). MTX AUC0-t and AUC0-∞ also increased in low-dose borneol group, but the difference was not statistically significant (P> 0.05). Conclusion Natural borneol can increase the distribution of MTX in brain tissue of C6 glioma model rats and increase its bioavailability in brain tissue.