ENDOTHELIN-1 IS INVOLVED IN THE PATHOGENESIS OF ISCHEMIA/REPERFUSION LIVER-INJURY BY HEPATIC MICROCIRCULATORY DISTURBANCES
ENDOTHELIN-1 IS INVOLVED IN THE PATHOGENESIS OF ISCHEMIA/REPERFUSION LIVER-INJURY BY HEPATIC MICROCIRCULATORY DISTURBANCES
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DOI：
10.1002/hep.1840190319
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发表时间：
1994-03-01
期刊：
影响因子：
13.5
通讯作者：
KAMADA, T
中科院分区：
文献类型：
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作者：
GOTO, M;TAKEI, Y;KAMADA, T
肝缺血再灌注后出现微循环障碍。内皮素-1是一种有效的血管收缩肽，已知其调节局部循环。本研究旨在探讨内皮素-1（ET-1）是否参与肝脏缺血再灌注后微循环障碍和损伤的机制。在肝脏的正中和左侧叶缺血诱导60分钟，然后再灌注24 hr. In一些大鼠，内皮素-1抗血清或对照血清没有内皮素-1阻断活性静脉注射前再灌注。将大鼠分为缺血再灌注组、内皮素-1抗血清治疗组和假手术组。采用夹心酶免疫分析法测定缺血/再灌注前后肝上腔静脉血中内皮素-1的浓度。采用器官反射分光光度法测定再灌注前、再灌注后5 min、1、2、24 h局部肝组织血容量指数和局部肝组织血氧指数。缺血/再灌注组内皮素-1浓度在再灌注开始时立即从基础值1 pg/ml左右开始上升，再灌注后5 min达到5 ~ 6 pg/ml的值;与假手术组相比，再灌注期间内皮素-1浓度维持在显著高水平。缺血再灌注组在再灌注早期出现肝微循环障碍，表现为肝组织血容量指数和血氧指数降低。注射内皮素-1抗血清可明显减轻缺血/再灌注后肝脏微循环障碍。再灌注2小时，ET-1抗血清治疗组血清ALT水平较未治疗组下降40%~ 50%。此外，内皮素-1抗血清治疗组的肝损伤组织学评估显着减少。总之，内皮素-1似乎参与了缺血/再灌注后肝脏微循环障碍和组织学损伤。阻断内皮素-1的作用可以防止缺血/再灌注后的肝损伤。
Hepatic microcirculatory perturbation is observed after ischemia/reperfusion. Endothelin-1, a potent va- soconstrictive peptide, is known to modulate local circulation. This study was designed to examine whether endothelin-1 participates in the mechanism of microcirculatory disturbance and damage of the liver after ischemia/reperfusion. Ischemia in the median and left lateral lobes of the liver was induced for 60 min; it was followed by reperfusion for 24 hr. In some rats, endothelin-1 antiserum or control serum without endothelin-1-blocking activity was administered intravenously just before reperfusion. Rats were divided into three groups: an ischemia/reperfusion group that was injected with control serum, an endothelin-1 antiserum-treated group and a sham-operated group. Endothelin-1 concentrations in blood collected from the suprahepatic vena cava were measured before and after ischemia/reperfusion by use of a sandwich enzyme immunoassay. Index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue were assessed with an organ reflectance spectrophotometry system before and at 5 min and 1, 2, and 24 hr after reperfusion. The endothelin-1 concentration in the ischemia/reperfusion group started to rise immediately at onset of reperfusion from basal values around 1 pg/ml and reached a value of 5 to 6 pg/ml 5 min after reperfusion; it was maintained at significantly high levels during the reperfusion period compared with the sham-operated group. Hepatic microcirculatory disturbance indicated by lowered index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue levels was observed in the early phase of reperfusion in the ischemia/reperfusion group. Endothelin-1 antiserum injection diminished significantly the microcirculatory disturbance in the liver after ischemia/reperfusion. The serum ALT levels in the endothelin-1 antiserum-treated group 2 hr reperfusion were decreased by 40% to 50% compared with the nontreated group. Moreover, liver damage assessed histologically was reduced dramatically in the endothelin-1 antiserum-treated group. In conclusion, endothelin-1 appears to be involved in the microcirculatory disturbance and histological damage in the liver after ischemia/reperfusion. Blockade of endothelin-1 action may prevent liver injury after ischemia/reperfusion.