[原著］Bile endothelin-1 as a tool for diagnosig ischemia-reperfusion injury
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概要
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We investigated whether the extent of graft ischemia reperfusion (I/R) injury can be evaluated by assessing the level of bile and serum endothelin-1 (ET-1). In groups 1 to 3 (n=5 in each group), the livers of male Wistar rats were surgically isolated from the surrounding attachments and then perfused in-situ with heparinized cold saline (4℃) under a port-systemic shunt. The livers were then reperfused after a pre-determined cold ischemia time (0, 30, and 60 min in groups 1, 2, and 3, respectively). The ET-1 levels in either the bile or the serum obtained from the suprahepatic vena cava (SHVC) and abdominal aorta, were assessed from -1 hour to +72 hours after reperfusion in each group. In group 3, the ET-1 level at the SHVC increased to $19.9 \pm 2.88$ and $19.43 \pm 3.14$ pg/ml at 1.5 and 2 hr after reperfusion, respectively, which were significantly higher than those of group 1 ($13.6 \pm 2.73$, $13.05 0.58\pm $, p<0.05) and 2 ($11.67 \pm 2.21$, $12.2 \pm 2.22$, p<0.05). The bile ET-1 concentration in group 3 decreased at 1 hr after reperfusion ($14.22 \pm 6.26$ pg/ml), but increased in group 1 ($108.1 \pm 49.3$). The bile ET-1 concentration did not recover to its pre-ischemic level until 72 hr after reperfusion in group 3, but showed no apparent decrease throughout the experiment in groups 1 and 2. In immunohistochemistry, ET-1 expression on the central and portal vein was stronger in group 3 than in group 1, whereas the expression on the bile duct was weaker in group 3 than that in group 1. In conclusion, ET-1 was directly released from the damaged endothelial cells into the SHVC depending on the extent of the I/R injury, whereas the ET-1 excretion into the bile was inversely suppressed depending on the amount of I/R injury. These changes of ET-1 excretion might thus be useful in diagnosing hepatic I/R injury.
- 琉球医学会,Ryukyu Medical Associationの論文