Wang M, Sakon M, Miyoshi H, Umeshita K, Kishimoto S, Taniguchi K, Gotoh M, Imajoh-Ohmi S, Monden M
Department of Surgery II, Osaka University Medical School, 2-2 Yamadaoka, Osaka, Suita, 565, Japan.
J Surg Res. 1997 Dec;73(2):101-6. doi: 10.1006/jsre.1997.5200.
Prostaglandin I2 has a protective effect on hepatic ischemia-reperfusion injury. However, the exact intracellular mechanisms of this effect have not been elucidated. Calpain micro, a Ca2+-dependent protease, has been found to play a role in the ischemia-reperfusion injury of various organs. The hilar area of the left lateral and median lobes of rat livers was clamped for 60 min. A prostaglandin I2 analog (OP2507, C35H41NO4) was intravenously administered at 0.1, 0.32, or 1.0 microg/kg/min from 20 min before the ischemia. In addition to biochemical and microscopic analyses, the activation of calpain mu was investigated using specific antibodies against the intermediate (activated) and preactivated forms of calpain mu. The degradation of talin was also studied by Western blotting. When OP2507 was infused at 0.32 and 1.0 microg/kg/min, bile flow significantly increased after reperfusion compared with the control group, consistent with the decrease in serum transaminase levels. Membrane bleb formation and the appearance of the intermediate form of calpain mu were observed at 60 min of ischemia in the control and OP2507 (0.1 microg/kg/min) groups and remained present until 120 min after reperfusion. OP2507 (1.0 microg/kg/min) markedly suppressed not only membrane bleb formation but also calpain mu activation and the degradation of talin. In conclusion, OP2507 suppresses ischemia-reperfusion injury of the rat liver, and its cytoprotective effect is closely associated with the inhibition of calpain mu activation.
前列环素I2对肝脏缺血再灌注损伤具有保护作用。然而，这种作用的确切细胞内机制尚未阐明。钙蛋白酶μ，一种钙依赖性蛋白酶，已被发现在各种器官的缺血再灌注损伤中起作用。将大鼠肝脏左外叶和中叶的肝门区域夹闭60分钟。在缺血前20分钟开始，以0.1、0.32或1.0微克/千克/分钟的剂量静脉注射前列环素I2类似物（OP2507，C35H41NO4）。除了生化和显微镜分析外，还使用针对钙蛋白酶μ的中间（活化）形式和预活化形式的特异性抗体研究了钙蛋白酶μ的激活情况。还通过蛋白质免疫印迹法研究了踝蛋白的降解。当以0.32和1.0微克/千克/分钟的剂量输注OP2507时，与对照组相比，再灌注后胆汁流量显著增加，这与血清转氨酶水平的降低一致。在对照组和OP2507（0.1微克/千克/分钟）组中，在缺血60分钟时观察到膜泡形成和钙蛋白酶μ中间形式的出现，并一直持续到再灌注后120分钟。OP2507（1.0微克/千克/分钟）不仅显著抑制了膜泡形成，还抑制了钙蛋白酶μ的激活和踝蛋白的降解。总之，OP2507可抑制大鼠肝脏的缺血再灌注损伤，其细胞保护作用与抑制钙蛋白酶μ的激活密切相关。
