临时阻断兔肝循环肝动脉灌注的初步观察
림시조단토간순배간동맥관주적초보관찰
Preliminary observation on hepatic arterial infusion under temporary hepatic circulation occlusion in rabbits
  • 万方数据
    中华肿瘤杂志 중화종류잡지
    CHINESE JOURNAL OF ONCOLOGY
    2015年 2期 91-94 ,共4页

    刘鑫%熊玲%徐锐%曹喜才

    류흠%웅령%서예%조희재

    兔%动物实验%血药浓度%化学疗法,肿瘤,局部灌注%肝动脉灌注%临时阻断肝循环肝动脉灌注 兔%動物實驗%血藥濃度%化學療法,腫瘤,跼部灌註%肝動脈灌註%臨時阻斷肝循環肝動脈灌註
    토%동물실험%혈약농도%화학요법,종류,국부관주%간동맥관주%림시조단간순배간동맥관주
    Rabbits%Animal experimentation%Plasma concentration%Chemotherapy,cancer,regional perfusion%Hepatic artery infusion%Hepatic artery infusion under temporary hepatic circulation occlusion
    目的：初步探讨临时阻断肝循环肝动脉灌注（ HAI?THCO）的可行性、优势及局限性。方法12只实验兔随机分为肝动脉灌注组（ HAI组）和临时阻断肝循环肝动脉灌注组（ HAI?THCO组），每组6只。 HAI组经肝固有动脉灌注氟尿嘧啶（5?Fu，浓度10 mg／ml，剂量100 mg／kg）10 min， HAI?THCO组在灌注5?Fu的同时临时阻断入肝血流15 min。两组实验兔均于灌注开始后2、5、10、15、20、30 min采集肝循环及体循环血样各1 ml，高速离心后取上清液0．5 ml，采用高效液相色谱法进行血药浓度测定。结果 HAI组灌注后2、5、10、15 min，肝循环的血药浓度分别为（3．183±0．612）μg／ml、（4．408±1．092）μg／ml、（3．689±0．935）μg／ml和（1．965±0．514）μg／ml，体循环的血药浓度分别为（2．083±0．523）μg／ml、（2．335±0．669）μg／ml、（2．190±0．517）μg／ml和（1．717±0．529）μg／ml，差异均有统计学意义（均P＜0．05）；但HAI组灌注后20、30 min，肝循环的血药浓度分别为（1．637±0．331）μg／ml和（1．453±0．254）μg／ml，体循环的血药浓度分别为（1．525±0．424）μg／ml和（1．419±0．471）μg／ml，差异均无统计学意义（均P＞0．05）。 HAI?THCO组灌注后2、5、10、15、20、30 min，肝循环的血药浓度分别为（18．494±2．794）μg／ml、（21．898±2．768）μg／ml、（23．057±3．270）μg／ml、（15．222±2．843）μg／ml、（7．947±0．877）μg／ml和（1．585±0．417）μg／ml，体循环的血药浓度分别为（0．885±0．137）μg／ml、（0．973±0．124）μg／ml、（1．456±0．217）μg／ml、（1．005±0．220）μg／ml、（1．232±0．140）μg／ml和（1．049±0．133）μg／ml，差异均有统计学意义（均P＜0．05）。 HAI?THCO组灌注后所有时间点肝循环的血药浓度均高于HAI组（均P＜0．05），而HAI?THCO组灌注后所有时间点体循环的血药浓度均低于HAI组（均P＜0．05）。 HAI?THCO组和HAI组肝循环的血药浓度峰值（Cmax）分别为（23．057±3．270）μg／ml和（4．408±1．092）μg／ml（P＜0．001），体循环的Cmax分别为（1．456±0．217）μg／ml和（2．335±0．669）μg／ml（P＝0．022）。 HAI?THCO组和HAI组肝循环的浓度?时间曲线下面积（AUC）分别为（368．927±52．416）μg·min·ml－1和（65．630±14．928）μg·min·ml－1（P＜0．001），体循环的AUC分别为（27．193±3．948）μg·min·ml－1和（45．301±12．275）μg·min·ml－1（P＝0．014）。结论 HAI?THCO不仅可以增加肝脏局部血药浓度，延长药物作用时间，还可以降低体循环血药浓度，在提高化疗效果的同时可明显降低系统毒性。
    목적：초보탐토림시조단간순배간동맥관주（ HAI?THCO）적가행성、우세급국한성。방법12지실험토수궤분위간동맥관주조（ HAI조）화림시조단간순배간동맥관주조（ HAI?THCO조），매조6지。 HAI조경간고유동맥관주불뇨밀정（5?Fu，농도10 mg／ml，제량100 mg／kg）10 min， HAI?THCO조재관주5?Fu적동시림시조단입간혈류15 min。량조실험토균우관주개시후2、5、10、15、20、30 min채집간순배급체순배혈양각1 ml，고속리심후취상청액0．5 ml，채용고효액상색보법진행혈약농도측정。결과 HAI조관주후2、5、10、15 min，간순배적혈약농도분별위（3．183±0．612）μg／ml、（4．408±1．092）μg／ml、（3．689±0．935）μg／ml화（1．965±0．514）μg／ml，체순배적혈약농도분별위（2．083±0．523）μg／ml、（2．335±0．669）μg／ml、（2．190±0．517）μg／ml화（1．717±0．529）μg／ml，차이균유통계학의의（균P＜0．05）；단HAI조관주후20、30 min，간순배적혈약농도분별위（1．637±0．331）μg／ml화（1．453±0．254）μg／ml，체순배적혈약농도분별위（1．525±0．424）μg／ml화（1．419±0．471）μg／ml，차이균무통계학의의（균P＞0．05）。 HAI?THCO조관주후2、5、10、15、20、30 min，간순배적혈약농도분별위（18．494±2．794）μg／ml、（21．898±2．768）μg／ml、（23．057±3．270）μg／ml、（15．222±2．843）μg／ml、（7．947±0．877）μg／ml화（1．585±0．417）μg／ml，체순배적혈약농도분별위（0．885±0．137）μg／ml、（0．973±0．124）μg／ml、（1．456±0．217）μg／ml、（1．005±0．220）μg／ml、（1．232±0．140）μg／ml화（1．049±0．133）μg／ml，차이균유통계학의의（균P＜0．05）。 HAI?THCO조관주후소유시간점간순배적혈약농도균고우HAI조（균P＜0．05），이HAI?THCO조관주후소유시간점체순배적혈약농도균저우HAI조（균P＜0．05）。 HAI?THCO조화HAI조간순배적혈약농도봉치（Cmax）분별위（23．057±3．270）μg／ml화（4．408±1．092）μg／ml（P＜0．001），체순배적Cmax분별위（1．456±0．217）μg／ml화（2．335±0．669）μg／ml（P＝0．022）。 HAI?THCO조화HAI조간순배적농도?시간곡선하면적（AUC）분별위（368．927±52．416）μg·min·ml－1화（65．630±14．928）μg·min·ml－1（P＜0．001），체순배적AUC분별위（27．193±3．948）μg·min·ml－1화（45．301±12．275）μg·min·ml－1（P＝0．014）。결론 HAI?THCO불부가이증가간장국부혈약농도，연장약물작용시간，환가이강저체순배혈약농도，재제고화료효과적동시가명현강저계통독성。
    Objective To explore the advantages, feasibility and limitations of hepatic arterial infusion under temporary hepatic circulation occlusion. Methods Twelve rabbits were randomly divided into two groups: hepatic artery infusion group ( HAI group ) and hepatic artery infusion under temporary hepatic circulation occlusion group (HAI?THCO). Microcatheters were separately inserted into the proper hepatic artery and right hepatic vein. For the HAI group, 5?Fu (10 mg/ml and 100 mg/kg) was infused into the common hepatic artery with a high pressure injector for 10 minutes. For the HAI?THCO group, the common hepatic artery and hepatic portal vein were temporarily occluded for 15 minutes using artery clamp when 5?Fu was being infused. For the two groups, at 2, 5, 10, 15, 20 and 30 min after the start of infusion, blood samples of the hepatic flow were collected from the right hepatic vein and of the systemic blood flow from the inferior vena cava, 1 ml at each time point. The blood drug concentration of these blood samples was determined by high performance liquid chromatography (HPLC). Results Except that at 20 and 30 min after infusion, in the HAI group, the blood drug concentration of hepatic circulation was significantly higher than that of systemic circulation (P<0. 05). But in the HAI?THCO group, the blood drug concentration of hepatic circulation was significantly higher than that of systemic circulation at all the time points (P <0. 05). The hepatic circulation blood drug level of the HAI?THCO group was always significantly higher than that of the HAI group (P < 0. 05), but the systemic circulation blood drug concentration of the HAI?THCO group was always lower (P <0. 05). The hepatic circulation maximum concentration (Cmax) of blood drug concentration of the HAI?THCO and HAI groups was (23. 057 ± 3. 270)μg/ml and (4. 408 ± 1. 092)μg/ml, respectively, and the Cmax of HAI?THCO group was significantly higher (P<0. 001), being 5. 23 times of that of HAI group. The systemic circulation Cmax of the two groups was (1. 456 ± 0. 217) μg/ml and (2. 335 ± 0. 669) μg/ml, respectively, and the Cmax of HAI group was 1. 60 times higher than that of the HAI?THCO group (P=0. 022). The hepatic circulation AUC of HAI?THCO and HAI groups was (368. 927 ± 52. 416)μg·min·ml-1 and (65. 630 ± 14. 928)μg·min·ml-1, respectively. The AUC of HAI?THCO group was 5. 62 times higher than that of the HAI group (P<0. 001). The systemic circulation AUC of the two groups was (27. 193 ± 3. 948)μg·min·ml-1 and (45. 301 ± 12. 275) μg·min·ml-1, respectively. The AUC of HAI group was 1. 67 times higher than that of the HAI?THCO group (P =0. 014). Conclusions HAI?THCO is a simple and effective regional hepatic infusion chemotherapy technique. It can be performed through occluding the common hepatic artery and the hepatic portal vein by balloon catheter. HAI?THCO can not only increase the blood drug concentration in the hepatic circulation, but also decrease the blood drug concentration in the systemic circulation, therefore, distinctly lowering the systemic toxicity.
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