肝动脉灌注和外周静脉输注5-FU在大鼠肝脏和血液中的浓度分布的实验研究

Study on distribution of 5-FU in the liver and blood during hepatic arterial perfusion and peripheral venous infusion in rats

目的探讨经肝动脉区域灌注和外周静脉注射5-FU在大鼠血液和肝脏组织中的浓度分布规律及差异。方法本研究将24只Wistar大鼠随机分为两组:A组为肝动脉灌注组;B组为外周静脉(颈静脉)输注组,分别经肝动脉插管区域灌注与经颈静脉注射5-FU,剂量为20mg/kg体重,每组均有6只大鼠取血,6只取肝组织样本。采用高效液相色谱法测定血浆及肝脏组织中5-FU的含量,并计算5-FU在肝脏和血浆中的药动学参数、穿透比率、穿透指数和相对治疗优势度。结果经外周静脉注射后肝脏组织的药物峰浓度(Cmax)和药物时量曲线下面积(AUC)分别为13.79±4.56μg/g,342.20±108.20μg·h/g;血浆Cmax和AUC分别为36.85±5.96μg/ml,842.00±158.00μg·h/ml。肝动脉灌注5-FU后肝脏组织药物Cmax和AUC分别为29.58±4.30μg/g,794.60±115.40μg·h/g;血浆Cmax和AUC分别为24.39±4.63μg/ml,639.70±133.80μg·h/ml。结论与外周静脉注射全身化疗比较,区域性肝动脉灌注5-FU可显著提高肝脏组织中的药物浓度,同时减少化疗药物在外周血中的分布。

Objective To study the distribution and difference of 5-FU in the liver and blood during hepatic arterial perfusion and peripheral venous infusion in rats. Method Twenty-four Wistar rats were divided into two groups randomly： A. hepatic artery group, B. systemic vein group. To fulfil the systemic venous bolus injection, jugular vein was catheterized. Also hepatic artery was catheterized to perfuse 5-FU. The dose was 20 mg/kg. In each group, the blood was sampled in six rats and the liver was sampled in the other six rats among them. High performance liquid chromatography was adopted to measure the content of 5-FU in piasma and liver tissue. Then the pharmacokinetie parameters, penetration rate, penetration index and therapeutics dominancy of 5-FU were calculated. Result Through the systemic vein route, the peak concention （Cmax）and time-quality area under curve （AUC）of liver tissue were as followed：13.79±4.56 μg/g, 342.20±108.20 μg·h/g;and the plasma Cmax and AUC were 36.85±5.96 μg/ml, 842.00±158.00 μg·h/ml. Through the hepatic artery route, the Cmax and AUC of liver tissue were 29.58±4.30 μg/g,794.60±115.40 μg·h/g, and the Cmax and AUC of plasma were 24.39±4.63 μg/ml,639.70±133.80 μg·h/ml. Conclusion Compared with systemic venous bolus injection of 5-FU, locoregional hepatic artery perfusion could significantly increase the concentration of chemotherapy agent in liver tissue, and decrease the drug distribution in peripheral blood.