Luo B, Abrams G A, Fallon M B
Department of Internal Medicine and Liver Center, University of Alabama at Birmingham, 35294-0007, USA.
J Hepatol. 1998 Oct;29(4):571-8. doi: 10.1016/s0168-8278(98)80152-9.
BACKGROUND/AIMS: Models of hepatopulmonary syndrome require both hepatic injury and portal hypertension to develop pulmonary microvascular and gas exchange abnormalities. Recently, increased endothelin-1 levels associated with vasodilatation, have been observed in cirrhosis. We investigated endothelin-1 production in common bile duct ligated animals with hepatopulmonary syndrome in comparison to partial portal vein ligated animals that do not develop hepatopulmonary syndrome.
Organ and plasma endothelin-1 were measured in sham, bile duct ligated and portal vein ligated rats, and Northern analysis and immunohistochemistry were performed in liver. Plasma endothelin-1 levels were correlated with pulmonary endothelial nitric oxide synthase levels and alveolar-arterial oxygen gradients.
Hepatic and plasma endothelin-1 increased only after bile duct ligation, and were accompanied by increased hepatic endothelin-1 mRNA and increased endothelin-1 protein in biliary epithelium. Plasma endothelin-1 levels correlated directly with both pulmonary endothelial nitric oxide synthase levels and alveolar-arterial gradients.
Enhanced hepatic production and increased plasma levels of endothelin-1 occur after bile duct ligation, but not after portal vein ligation, and correlate with associated molecular and gas exchange alterations in the lung. Endothelin-1 may contribute to the pathogenesis of hepatopulmonary syndrome.
背景/目的：肝肺综合征模型需要肝损伤和门静脉高压同时存在，才能引发肺微血管和气体交换异常。最近，在肝硬化患者中观察到内皮素-1水平升高与血管舒张有关。我们研究了与未发生肝肺综合征的部分门静脉结扎动物相比，胆总管结扎诱发肝肺综合征动物体内内皮素-1的产生情况。
测定假手术组、胆总管结扎组和门静脉结扎组大鼠的器官和血浆内皮素-1水平，并对肝脏进行Northern分析和免疫组织化学检测。血浆内皮素-1水平与肺内皮型一氧化氮合酶水平及肺泡-动脉氧梯度相关。
仅在胆总管结扎后，肝脏和血浆内皮素-1水平升高，并伴有肝内皮素-1 mRNA增加和胆管上皮细胞内皮素-1蛋白增加。血浆内皮素-1水平与肺内皮型一氧化氮合酶水平和肺泡-动脉梯度均呈正相关。
胆总管结扎后肝脏内皮素-1生成增强且血浆水平升高，而门静脉结扎后则无此现象，且与肺内相关分子改变和气体交换改变相关。内皮素-1可能参与肝肺综合征的发病机制。
