Kobayashi Mitsunobu, Takeyoshi Izumi, Kurabayashi Makoto, Matsumoto Koshi, Morishita Yasuo
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Hepatogastroenterology. 2007 Mar;54(74):522-6.
BACKGROUND/AIMS: This study was designed to investigate the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the rat liver.
Male Sprague-Dawley rats were used in this experimental study. Total hepatic ischemia was induced with a clamping portal triad. The animals were divided into two groups: the control group and the FK group, in which FK3311 (FK, 1.0 mg/kg) was administered via the penile vein. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured 2 h after reperfusion, while those of thromboxane (Tx) B2 and 6-ketoprostaglandin (PG) F1alpha (stable metabolites of TxA2 and PGI2) were measured 30 min after reperfusion. The liver tissue blood flow was measured at preischemia, end-ischemia, and 30, 60, 90, and 120 min after reperfusion. The liver tissues obtained from animals at 2h after reperfusion were excised for histopathology.
The serum levels of AST, ALT, and LDH were significantly lower in the FK group than in the control group. Similarly, in the FK group, the serum levels of TxB2 were significantly lower than in the control group. By contrast, the 6-keto-PG F1a levels were not significantly reduced. The liver tissue blood flow at 120 min after reperfusion was significantly higher in the FK group than in the control group. The histopathological study showed that hepatic tissue damage was milder in the FK group than in the control group.
FK has protective effects on hepatic ischemia-reperfusion injury stemming from the marked inhibition of TxA2.
背景/目的：本研究旨在探讨选择性环氧化酶-2抑制剂FK3311对大鼠肝脏热缺血再灌注损伤的影响。
本实验研究采用雄性Sprague-Dawley大鼠。通过夹闭门静脉三联诱导全肝缺血。动物分为两组：对照组和FK组，FK组经阴茎静脉给予FK3311（FK，1.0mg/kg）。再灌注2小时后测定血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和乳酸脱氢酶（LDH）水平，再灌注30分钟后测定血栓素（Tx）B2和6-酮前列腺素（PG）F1α（TxA2和PGI2的稳定代谢产物）水平。在缺血前、缺血末以及再灌注后30、60、90和120分钟测量肝组织血流量。取再灌注2小时后动物的肝脏组织进行组织病理学检查。
FK组血清AST、ALT和LDH水平显著低于对照组。同样，FK组血清TxB2水平显著低于对照组。相比之下，6-酮-PG F1α水平未显著降低。FK组再灌注120分钟时的肝组织血流量显著高于对照组。组织病理学研究表明，FK组肝组织损伤比对照组轻。
FK对肝缺血再灌注损伤具有保护作用，其机制可能是通过显著抑制TxA2实现的。
