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目的探讨尼莫地平(Nim)对胶质瘤细胞及荷瘤大鼠替尼泊苷(Ten)的浓度及药效学的影响。方法 WST-1法测定Ten的IC50和Nim的安全浓度,选用此浓度进行实验,判断药物合用是否有协同作用。分为单独应用Ten和联用Nim组,体外细胞采用溶涨法破膜,测定细胞液内Ten的浓度;荷瘤大鼠测定血浆和脑组织中Ten的浓度,Ten含量测定采用HPLC-MS/MS。结果联合应用Nim的C6细胞用药48h细胞液中Ten的浓度是单独用药的10倍以上,荷瘤大鼠测定血浆浓度联合用药为155.02μg·L-1,单独用药为72.25μg·L-1。正常脑组织部分浓度相差不大。结论 Nim可明显增加细胞内和荷瘤大鼠血浆中化疗药物Ten的浓度,明显增强抗肿瘤作用。为临床胶质瘤病人联合用药提供理论依据。
Objective To investigate the effect of nimodipine on the concentration and pharmacodynamics of glioma cells and tumor-bearing rats. Methods The WST-1 method was used to determine the IC50 and Nim concentrations in Ten. The concentration was used to determine whether the combination of drugs had synergistic effect. Divided into Ten and combined with Nim group alone, in vitro cells by swelling rupture of membranes, determination of the concentration of Ten within the cytosol; Tumor-bearing rats measured in plasma and brain tissue Ten concentration, determination of Ten content by HPLC-MS / MS. Results The concentration of Ten in 48h cells treated with Nim was more than 10 times higher than that of the control alone. The combined plasma concentration of the drug was 155.02μg · L-1 for the tumor-bearing rats and 72.25μg · L-1 for the drug alone. Normal brain tissue concentration is not much difference. Conclusion Nim can significantly increase the concentration of chemotherapeutic drug Ten in the plasma and the tumor-bearing rats, and significantly enhance the antitumor effect. To provide a theoretical basis for the combination of clinical glioma patients.