前列环素类似物（OP - 2507）可减轻大鼠再灌注损伤模型中的肝微循环紊乱、能量耗竭和脂质过氧化。

Prostacyclin analogue (OP-2507) attenuates hepatic microcirculatory derangement, energy depletion, and lipid peroxidation in a rat model of reperfusion injury.

作者信息

Chen H M, Chen M F, Shyr M H

机构信息

Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China.

出版信息

J Surg Res. 1998 Dec;80(2):333-8. doi: 10.1006/jsre.1998.5425.

DOI:10.1006/jsre.1998.5425

PMID:9878334

Abstract

BACKGROUND

Microcirculatory derangement, energy depletion, and lipid peroxidation are associated with the development of ischemia-reperfusion injury in the liver. This study investigated the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury.

MATERIALS AND METHODS

Adult, male Sprague-Dawley rats were divided into four treatment groups: (1) sham-operated control (laparotomy only, no ischemia), N =6; (2) ischemia control (1 h ischemia, 2 h reperfusion), N = 6; (3) intravenous infusion with OP-2507 ([15-cis-14-propylcyclohexyl]-16, 17,18,19,20-pentanor-9-deoxy-9a,6-nitrilo-PGF, methyl ether; Ono Pharmaceutical Co, Ltd, Osaka, Japan) at a dose of 1 microg/kg/min plus ischemia (1 h ischemia, 2 h reperfusion), N = 6; and (4) intravenous infusion with OP-2507 at a dose of 0.1 microg/kg/min plus ischemia (1 h ischemia, 2 h reperfusion), N = 6. A laser-Doppler flowmeter and in vivo microscopy were used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) levels were determined at the end of the experiment.

RESULTS

Compared with ischemia alone, OP-2507 significantly reduced the extent of microcirculatory and hemodynamic derangement following ischemia-reperfusion. The changes of mean systolic arterial pressure (MSAP) following ischemia-reperfusion showed biphasic alterations. OP-2507 at both doses significantly attenuated decreases in MSAP. OP-2507 lessened adherent leukocyte count and improved flow velocity in the sinusoids and postsinusoidal venules. OP-2507 at the dose of 1 microg/kg/min reduced MDA (1.04 +/- 0.27 micromol/g protein vs 2.64 +/- 0.59 micromol/g protein in the ischemia and reperfusion group) and increased ATP levels (2.03 +/- 0.17 micromol/g wet wt vs 0.73 +/- 0.21 micromol/g wet wt in the ischemia and reperfusion group), while OP-2507 at a smaller dose (0. 1 microg/kg/min) had lesser but significant effects on MDA and ATP alterations.

CONCLUSION

This study demonstrates that OP-2507 treatment of ischemia can ameliorate ischemia-reperfusion injury of the rat liver.

摘要

背景

微循环紊乱、能量耗竭和脂质过氧化与肝脏缺血再灌注损伤的发生有关。本研究调查了一种前列环素类似物（OP - 2507）对肝脏缺血再灌注损伤的影响。

材料与方法

成年雄性Sprague - Dawley大鼠分为四个治疗组：（1）假手术对照组（仅开腹，无缺血），N = 6；（2）缺血对照组（缺血1小时，再灌注2小时），N = 6；（3）静脉输注OP - 2507（[15 - 顺式 - 14 - 丙基环己基]-16,17,18,19,20 - 五降 - 9 - 脱氧 - 9α,6 - 腈基 - PGF，甲醚；日本大阪小野制药有限公司），剂量为1微克/千克/分钟加缺血（缺血1小时，再灌注2小时），N = 6；（4）静脉输注OP - 2507，剂量为0.1微克/千克/分钟加缺血（缺血1小时，再灌注2小时），N = 6。使用激光多普勒血流仪和体内显微镜检查来研究肝脏微循环。在实验结束时测定组织丙二醛（MDA）和三磷酸腺苷（ATP）水平。

结果

与单纯缺血相比，OP - 2507显著减轻了缺血再灌注后微循环和血流动力学紊乱的程度。缺血再灌注后平均收缩动脉压（MSAP）的变化呈双相改变。两种剂量的OP - 2507均显著减轻了MSAP的下降。OP - 2507减少了黏附白细胞计数，并改善了肝血窦和窦后小静脉的流速。1微克/千克/分钟剂量的OP - 2507降低了MDA（缺血再灌注组为2.64±0.59微摩尔/克蛋白质，该组为1.04±0.27微摩尔/克蛋白质）并提高了ATP水平（缺血再灌注组为0.73±0.21微摩尔/克湿重，该组为2.03±0.17微摩尔/克湿重），而较小剂量（0.1微克/千克/分钟）的OP - 2507对MDA和ATP改变的影响较小但具有显著意义。