摘要：
背景与目的：肝动脉、肝门静脉灌注区域化疗是肝癌的重要治疗手段，本研究探讨区域性灌注化疗时氟尿嘧啶(fluorouracil，5-FU)在大鼠肝癌和肝脏组织及血浆中的分布，为临床肝脏肿瘤化疗提供参考。方法：将24只荷瘤大鼠随机分为4组，分别经外周静脉(尾静脉)、肝动脉、肝门静脉或结扎肝动脉后经肝门静脉灌注5-FU，剂量为20 mg/kg。采用高效液相色谱法测定肝癌、肝脏组织及血浆中5-FU的含量，并计算药物在血浆、肝脏和肝癌组织间的穿透比率。结果：结扎肝动脉的肝门静脉组5-FU浓度在肝脏和肝癌组织中最高，分别为(22.1±9.5)μg/g和(16.4±7.2)μg/g；其次为肝动脉组；肝门静脉组5-FU浓度在肝癌组织中的浓度较低，为(8.9±3.7)μg/g；外周静脉组5-FU浓度在肝脏和肝癌组织中的药物浓度均为最低，肝癌组织中的浓度仅为(4.3±2.2)μg/g。在血浆中的5-FU浓度正好相反，外周静脉组浓度最高(26.8±12.5)μg/mL，肝动脉组(16.4±9.7)μg/mL、结扎肝动脉的肝门静脉组(15.9±10.1)μg/mL和肝门静脉组(14.9±8.5)μg/mL等3组浓度相近，均明显低于外周静脉组(P<0.05)。5-FU的肝癌/血浆穿透比率依次为结扎肝动脉的肝门静脉组(103.47%)，肝动脉组(92.94%)，肝门静脉组(59.58%)和外周静脉组(16.08%)。结论：与外周静脉注射全身化疗比较，区域性灌注化疗可显著提高肝癌和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，其中经结扎肝动脉的肝门静脉灌注和经肝动脉灌注是肝癌区域性化疗2种较好的途径。%Background and purpose: Locoregional infusion chemotherapy such as hepatic artery, or hepaticportal vein infusion is one of the most important treatments for hepatocelluar carcinoma. This study was aimed to investigate the distribution of fluorouracil(5-FU) in rat hepatoma, liver tissue and plasma after administrated by caudal vein or locoregional routes of hepatic artery, hepaticportal vein, and hepaticportal vein with ligated hepatic artery. Methods:Twenty-four tumor-bearing rats were divided into 4 groups randomly, and they were infused with 5-FU through peripheral vein(caudal vein), hepatic artery, hepaticportal vein or hepaticportal vein with ligated hepatic artery, which dose was 20 mg/kg. High performance liquid chromatography was adopted to measure the content of 5-FU in hepatoma, liver tissue and plasma, and the drug penetration rate among them were calculated. Results:The group of hepaticportal vein with ligated hepatic artery reached the highest concentrations of 5-FU in live tissue and hepatoma, which concentrations were (22.1±9.5)μg/g and (16.4±7.2)μg/g. Then was the hepatic artery group, and the concentration of the hepaticportal vein group in the hepatoma focus was much smaller than the former 2 groups, which was (8.9±3.7)μg/g. The peripheral vein group got the lowest concentrations both in the liver tissue and hepatoma, which were (9.4±3.7) and (4.3±2.2)μg/g. The concentrations of 5-FU in the plasma in the peripheral vein group, the hepatic artery group, the group of hepaticportal vein with ligated hepatic artery and the hepaticportal vein group were (26.8±12.5), (16.4±9.7), (15.9±10.1) and (14.9±8.5)μg/mL, which indicated that the drug concentrations of the latter 3 groups were much lower than the former group. The hepatoma/plasma penetration rate of 5-FU in the group of hepaticportal vein with ligated hepatic artery, the hepatic artery group, the hepaticportal vein group and the peripheral vein group were 103.47%, 92.94%, 59.58% and 16.08%. Conclusion: Compared to the peripheral venous bolus injection, locoregional infusion could significantly increase the concentrations of chemotherapy agent in hepatoma focus and liver tissue, and decrease the drug distributions in peripheral blood. And the infusion through hepaticportal vein with ligated hepatic artery and through hepatic artery reaches higher concentrations in the hepatoma focuses, which indicate that they are 2 practical and promising routes for the locoregional chemotherapy of hepatoma.
