目的 研究川芎挥发油体内配伍替莫唑胺对C6胶质瘤大鼠抗肿瘤效果及作用机制。方法 制备C6胶质瘤大鼠模型，对比替莫唑胺单独给药、川芎挥发油与替莫唑胺配伍给药后大鼠的体质量、生存状态、肿瘤体积的变化及抑瘤率；HPLC法测定替莫唑胺单独给药、川芎挥发油与替莫唑胺配伍给药后，替莫唑胺在胶质瘤U87-MG细胞内、外液中的浓度，并进行统计学分析；Western blotting法研究替莫唑胺单给药、川芎挥发油与替莫唑胺配伍给药后对U87-MG细胞P-糖蛋白（P-gp）表达的影响。结果 与替莫唑胺单独给药比较，川芎挥发油与替莫唑胺配伍给药后大鼠肿瘤体积显著减小（P<0.05），与川芎挥发油用量呈正相关，同时配伍组大鼠体质量上升趋势更快，生存状态较好。川芎挥发油可以促进替莫唑胺进入U87-MG细胞内液中，且随着挥发油浓度的增加，促进作用越强。其中6.25×10^-3 μL/mL川芎挥发油可显著增加替莫唑胺在细胞内液中的蓄积（P<0.05）。Western blotting实验结果表明，与替莫唑胺组比较，替莫唑胺和3.125×10^-3、6.250×10^-3 μL/mL川芎挥发油配伍后，可极显著降低P-gp蛋白的表达水平（P<0.01）。结论 川芎挥发油可通过下调P-gp蛋白的表达，促进替莫唑胺进入胶质瘤细胞内，发挥协同抗肿瘤作用。

Objective To investigate the anti-tumor effect of Ligusticum chuanxiong volatile oil in combination with temozolomide (TMZ) in the treatment of glioma, and illuminate its possible mechanism. Methods After C6 glioma animal model was successfully finished, changes of body weight, survival status, tumor volume, and the tumor inhibition rate of rats were detected in the TMZ group and the compatibility group of the volatile oil of L. chuanxiong and TMZ. The concentration of TMZ in the internal and external fluids of U87-MG cells was measured by HPLC after the administration of TMZ and the combination of volatile oil of L. chuanxiong and TMZ, and the differences of the content were analyzed statistically. Western blotting was used to study the effects of TMZ monotherapy, L. chuanxiong volatile oil and TMZ on the expression of P-gp protein of U87-MG cells.Results Compared with TMZ group, the tumor volume of rats in the compatibility group was significantly decreased (P<0.05), which was positively correlated with the amount of volatile oil. At the same time, the weight gain of the rats in the compatibility group was increased and the survival status was better. Volatile oil of L. chuanxiong can promote the entry of TMZ into U87-MG cells, and with the increase concentration of volatile oil, the promoting effect was stronger. Volatile oil at 6.25×10^-3 μL/mL can significantly increase the accumulation of TMZ in the internal fluid (P<0.05). Western blotting analysis showed that P-gp expressions of cells treated with combination treatment with TMZ (20 μg/mL) and volatile oil[(3.125×10^-3), (6.25×10^-3) μL/mL] were markedly down-regulated (P<0.01), when compared with TMZ group. Conclusion The volatile oil of L. chuanxiong can promote TMZ entry into glioma cells and then enhance TMZ-induced anticancer efficiency in vivo by inhibiting P-gp expression.

国家自然科学基金资助项目（8176140533）；江西省自然科学基金项目（20171BAB205093）；江西省博士后项目（2017KY08）；江西省卫生厅项目（2016A012）；江西中医药大学双一流学科项目（JXSYLXK-ZHYAO091）