急性淋巴细胞白血病小鼠甲氨蝶呤化疗后血及脑组织药物浓度的对比研究  

The comparison study of the relationship between blood concentration and brain tissue drug concentration of acute lymphoblastic leukemia mice by TMX chemotherapy

作　　者：金明卫[1] 薛天阳[1] 许伟[1] 高吉照[1] 

机构地区：[1]徐州医学院附属医院儿科,221000

出　　处：《白血病．淋巴瘤》2010年第5期297-300,共4页Journal of Leukemia & Lymphoma

摘　　要：目的 探索急性淋巴细胞白血病小鼠不同剂量甲氨蝶呤（MTX）化疗后血和脑组织药物浓度的关系.方法 4周龄清洁级普通昆明小鼠80只：建立急性淋巴细胞白血病小鼠模型,随机抽取20只小鼠经股骨取骨髓行骨髓细胞学检查作模型验证;依据MTX化疗剂量与标本采取时间点的不同将余60只急性淋巴细胞白血病小鼠分为六组,每组10只,分别为A、B、C、D、E、F组;各组均取0.5ml血液及0.4 g脑组织,血液离心,脑组织匀浆后离心,取上清用荧光偏振免疫方法 检测药物浓度.结果 A、B、C、D、E、F六组平均MTX血药浓度分别为（39.08±5.18）μmol/L、（15.86±1.02）μmol/L、（8.67±5.43）μmol/L、（68.29±5.19）μmol/L、（29.55±6.22）μmol/L、（13.98±1.12）μmol/L,组间比较差异有统计学意义（P〈0.05）;各组脑组织平均MTX浓度依次为：（1.05±0.26）μmol/L、（0.61±0.25）μmol/L、（0.48±0.25）μmol/L、（2.07±0.35）μmol/L、（1.27±0.21）μmol/L、（0.59±0.69）μmol/L,组间比较差异有统计学意义（P〈0.05）;六组血与脑组织药物浓度相关系数依次为：0.82、0.75、0.19、0.81、0.55、0.43.结论 急性淋巴细胞白血病小鼠经大剂量MTX（HD-MTX）方案化疗后,于0.5 h出现血及脑组织药物浓度峰值,5g/m^2较3g/m^2能更好地透过血脑屏障使脑组织药物浓度达到有效治疗浓度.Objective The purpose of this paper is to study the relationship between blood concentration and brain tissue drug concentration by different dose of TMX chemotherapy acute lymphoblastic leukemia in mice. Methods 4 weeks, health Kun Ming mice 80： establishment acute lymphoblastic leukemia mice model,20 mice were randomly selected to take the femur bone marrow biopsy bone marrow OK for model verification; the remaining 60 acute lymphoblastic leukemia mice were allocated randomly 6 groups of 10 mice in each group, respectively A, B, C, D, E, F groups. And collected blood 0.5 ml and brain tissue 0.4 g individually at 0.5 hour in every group. We used supernatant of centrifugation blood and brain homogenate to detected drug concentration by fluorescence polarization immunoassay. Results The mean blood concentration of MTX of six groups A, B, C, D, E, F are （39.08±5.18） μmol/L, （15.86±1.02）μmol/L, （8.67± 5.43）μmol/L, （68.29±5.19）μmol/L, （29.55±6.22）μmol/L, （13.98±1.12）μmol/L, respectively. Compared the mean blood concentration of MTX of each group there are statistical significance （P〈0.05）. The mean concentration of MTX of six groups in brain tissue are followed by A group （1.05±0.26）μmol/L, B group （0.61±0.25）μmol/L, C group （0.48±0.25）μmol/L, D group （2.07±0.35）μmol/L, E group （1.27±0.21）μmol/L, F group （0.59±0.69）μmol/L. Compared the mean concentration of MTX of each group in brain tissue there are statistical significance （P〈0.05）. MTX concentration in blood and in brain tissue of correlation coefficient followed by 0.82, 0.75, 0.19, 0.81, 0.55, 0.43. Conclusion The chemotherapy acute lymphoblastic leukemia mice of HDMTX scheme, the peak of blood concentration and brain tissue drug concentration is come after injected MTX 0.5 hour, MTX 5 g/m^2 is better permeation blood-brain barrier and more easy make brain tissue drug concentration to reach effectively therapeutic concentration than MTX 3 g/m^2.

关 键 词：白血病 淋巴细胞 急性 甲氨蝶呤 血药浓度 脑组织药物浓度 动物实验 

分 类 号：R733.71[医药卫生—肿瘤]