经肝动脉区域肝脏隔离灌注的研究

Experimental Study of Regional Isolated Hepatic Perfusion via Hepatic Artery

目的 研究幼猪经肝动脉区域隔离肝灌注的效果。 方法 14只幼猪随机分为2组:对照组(7只):采用经肝动脉灌注;实验组( 7只):左肝动脉及左肝静脉插管,进行左肝区域隔离肝灌注。灌注液为氨甲喋呤溶液(1mg/kg), 灌注时间为60min。于灌注5、10、20、30、45、60min时分别抽取外周血、肝脏灌注区域血、肝脏未灌注区域血(实验组)测定血药浓度; 灌注后切取左肝及右肝组织进行病理检查。 结果 在所有时间点, 实验组肝脏灌注区域氨甲蝶呤的血药浓度明显高于非灌注区和外周血(P<0. 01), 60min时最高, 达( 40. 211±3. 756 )μg/ml, 而非灌注区和外周血中仅为(1. 584±0. 347)μg/ml和(0. 773±0. 096)μg/ml。实验组灌注区域血药浓度均高于对照组肝脏血药浓度(P<0. 01), 60min时分别达(40. 211±3. 756)μg/ml和(4. 498±1. 643)μg/ml。实验组灌注区浓度-时间曲线下面积为218. 295μg/ml,而在对照组肝脏仅为260. 860μg/ml。病理检查提示两组灌注肝脏均有肝细胞浊肿、气球样细胞,但实验组肝脏灌注区域肝细胞坏死率为85. 7% (6 /7),明显高于对照组28. 6% (2 /7)。实验组肝脏未灌注区域无明显病理损害。 结论 动物实验证实经肝动脉区域隔离肝灌注是一种灌注及隔离效果好、肝功能损害小的区域化疗方法。

Objective To investigate the effectiveness of regional isolated hepatic perfusion via hepatic artery in a porcine model. Methods 14 pigs were divided into 2 groups randomly. The animals of control group and experimental group were respectively underwent hepatic artery infusion and regional isolated hepatic perfusion. Perfusate was the methotrexate solution,perfusion duration was 60 min. The drug concentration of blood sample from systemic circulation 5,10, 20, 30, 45, 60 min,hepatic perfused area and unperfused area(only in the experimental group)were assayed at different timepoint after the onset of perfusion. The tissue from left and right lobe of liver was resected for pathological examination at 60min after perfusion. Results The peak drug concentration in perfusion area of experimental group were 55 fold higher than in the systemic circulation, and 40 fold higher than in the control group; the peak drug concentration in systemic circulation of control group were 4 fold higher than in the experimental group; the peak drug concentration in the perfused area of control group were 5 fold higher than in the unperfused area of experimental group. The pathological examination indicated that there were cloudy swelling and balloon degeneration of hepatocytes in both groups and there were bleeding and hepatocyte necrosis in the perfused area of experimental group; no obvious harmful changing was observed in the unperfused area of experimental group. Conclusion Regional hepatic perfusion via hepatic artery is demonstrated as a feasibile regional chemotherapeutic method with good effect and mild hepatic function damage.