前列地尔对肝细胞癌动脉化疗栓塞后肝血流灌注的影响

The effect of alprostadil on hepatic perfusion after transarterial chemoembolization for hepatoceHular carcinoma

目的初步探讨前列地尔（PGE1）对肝细胞癌（HCC）经动脉化疗栓塞（TACE）后肝血流灌注的影响。方法连续搜集接受TACE初治的HCC患者64例，随机数字法分为对照组与PGE1组，每组32例。对照组接受常规TACE治疗，第1次TACE4周后复治；PGE1组于TACE后经外周静脉推注PGE1 1次／d，连续1周，用药量为0．4μg／kg。所有患者于术前1周、术后4周内行非瘤区肝CT灌注成像（CTPI），测量肝动脉灌注量（HAP）、门静脉灌注量（PVP）、肝总血流灌注量（TLP）、肝动脉灌注指数（HPI），TACE后不同时期肝灌注参数的组内比较采用单因素方差分析，对照组与PGE1组肝各灌注参数组间比较采用t检验。结果对照组术前1周、第1次术后、第2次术后的HAP分别为（0．18±0．08）、（0．22±0．09）、（0．32±0．10）ml·min^-1·ml^-1；PVP分别为（1．11±0．31）、（0．82±0．27）、（0．59±0．25）ml·min^-1·ml^-1；TLP分另9为（1．29±0．33）、（1．04±0．28）、（0．91±0．24）ml·min^-1·ml^-1；HPI分别为（14．31±6．36）％、（21．37±9．07）％、（36．67±13．42）％。TACE不同时间HAP、PVP、TLP、HPI组间差异均有统计学意义（F值分别为19．71、27．47、14．75、41．41，P值均〈0．05）。PGE，组术前1周、第1次术后4周、第2次术后4周的HAP分别为（0．17±0．08）、（0．20±0．08）、（0．26±0．08）ml·min^-1·ml^-1；PVP分另4为（1．09±0．36）、（1．03±0．40）、（0．91±0．41）ml·min^-1·ml^-1；TLP分另0为（1．26±0．38）、（1．23±0．40）、（1．17±0．44）ml·min^-1·ml^-1；HPI分别为（14．04±6．71）％、（17．26±7．86）％、（23．93±8．96）％。其中HAP与HPI组间差异有统计学意义（F值分别为10．78、13．05，P值均〈0．05），而PVP与TLP组间差异无统计学意义（F值分别为1．73、0．39，P值均〉0．05）。第1次术后对照组与PGE，组的PVP与TLP的组间差异有统计学意义（t值分别为-2．37、-2．14，P值均〈0．05），而HAP、HPI组间差异无统计学意义（t值分别为0．86、2．24，P值均〉0．05）；第2次术后对照组与PGE，组的HAP、PVP、TLP、HPI组间差异均有统计学意义（t值分别为2．55、-4．49、-3．41、5．09，P值均〈0．05）。结论TACE后肝PVP与TLP减少而HAP与HPI增加，PGE，能改善以PVP为主的肝血流灌注，有助于减轻TACE对非瘤区肝组织的损害。

Objective To investigate the role of alprostadil on hepatic perfusion after transarterial chemoembolization（ TACE ） for hepatocellular carcinoma. Methods Sixty-four consecutive patients with HCC were randomized to either treatment with PGE1 after TACE （treatment group, 32 cases ） or no additional treatment after TACE （ control group, 32 cases）. In PGE1 group, Lipo-PGE1 was administered intravenously once a day for total of seven days, once after completion of TACE. The dosage of Lipo-PGE1 was 0. 4 μg/kg and rate 0. 05 μg·kg^-1·min^-1. In control group, regular TACE was used. All patients underwent hepatic CT perfusion within 1 week before TACE and 4 weeks after TACE. The parameters of hepatic perfusion, including hepatic arterial perfusion value （HAP）, portal vein perfusion value （PVP）, total liver perfusion value （TLP）, and hepatic arterial perfusion index （HPI） were measured and compared. Chi-Square test was used for comparison of CT perfusion parameters in different stage, and t test was used for comparison of each CT perfusion parameter between two groups. Results In control group, HAP of pre- TACE, 4 weeks after first TACE, and 4 weeks after second TACE was （0. 18 ± 0. 08 ） , （0. 22 ± 0. 09 ） , （0.32±0.10） ml· min^-1·ml^-1, respectively. Likewise, PVP was （1.11± 0. 31） , （ 0. 82 ± 0. 27 ） , （0. 59± 0. 25） ml· min^-1·ml^-1, respectively, and TLP was （ 1.29± 0. 33）, （ 1.04 ±0. 28 ）, （ 0. 91 ± 0. 24） ml· min^-1·ml^-1, respectively, and HPI was （14. 31 ±6. 36）%, （21.37±9. 07）%, （36. 67 ±13.42）%, respectively. The perfusion parameters at different stages of TACE were statistically different （F = 19. 71,27. 47,14. 75,41.41, P 〈 0. 05 ）. In PGE1 group, HAP before TACE, after first TACE, and after second TACE was （0. 17 ±0. 08） , （0. 20 ±0. 08） , （0. 26±0. 08） ml· min^-1·ml^-1 respectively, and PVP was （ 1.09 ±0. 36）, （ 1.03 ±0. 40）, （0. 91±0. 41 ） ml· min^-1·ml^-1, respectively, and TLP was （1.26±0.38）, （1.23±0.40）, （1.17±0.44） ml· min^-1·ml^-1 respectively, and HPI was （ 14. 04 ± 6. 71 ） %, （ 17. 26 ± 7. 86） %, （23. 93 ± 8. 96） %, respectively. The difference of HAP and HPI at different stage of TACE was significant （ F = 10. 78, 13.05, P 〈 0. 05 ）, but there was no significant difference both PVP and TLP （ F = 1.73,0. 39, P 〉 0.05 ）. The difference of PVP and TLP between the control and PGE1 group was significant after first TACE（ t = - 2. 37, - 2. 14, P 〈 0. 05 ） and second TACE （ t = 2.55, - 4. 49, P 〈 0. 05 ） In addition, after the second TACE, the HAP and HPI were also significantly different （t = - 3.41,5.09, P 〈 0. 05 ）. Conclusions PVP and TLP decrease while HAP and HPI increase after TACE. Lipo-PGE1 improves hepatic perfusion after TACE, exerting its greatest effect by increasing portal vein perfusion. Consequently, treatment with Lipo-PGE1 appears to increase liver tissue perfusion and thereby alleviate injury induced by TACE.