Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats

内皮素(ET)-1参与了正常肝脏的缺血再灌注损伤。本研究旨在阐明ET-1在肝硬变状态下HIR损伤中的作用。肝硬变大鼠肝组织ET-1水平明显高于非肝硬变大鼠。间歇性肝缺血再灌流1、3、6h血浆和肝脏ET-1水平，再灌流1、3、6h血浆AST水平升高，60min肝缺血结束和再灌流后肝组织SO2水平下降，与持续性肝缺血动物相比明显受到抑制。持续肝缺血时应用非选择性内皮素受体拮抗剂可明显改善血浆AST水平和肝组织SO2值，减少肝窦充血，提高7d存活率。在部分肝切除术中，肝硬变中持续的肝脏缺血与微循环紊乱和产生更多的ET-1有关。在肝脏外科手术中，对ET-1产生的药理学调节可能有助于减轻缺血损伤的肝硬变的再灌注损伤。

Endothelin (ET)-1 contributes to hepatic ischemia and reperfusion (HIR) injury in normal liver. This study was conducted to clarify the role of ET-1 in HIR injury in cirrhotic state. Hepatic ET-1 levels in cirrhotic rats were significantly higher than those in non-cirrhotic rats. Plasma and hepatic ET-1 levels at 1, 3 and 6 hours of reperfusion animals subjected to intermittent hepatic ischemia, the elevation of plasma AST levels at 1, 3 and 6 hours of reperfusion and the decline in hepatic SO2 at the end of 60-minute hepatic ischemia and after reperfusion were significantly suppressed when compared to those subjected to continuous hepatic ischemia. Pretreatment with a non-selective endothelin receptor antagonist in continuous hepatic ischemia significantly ameliorated plasma AST levels and hepatic SO2 values with less hepatic sinusoidal congestion, resulting in an improvement in the 7-day survival rate. Continuous hepatic ischemia in the cirrhotic liver has disadvantages relating to microcirculatory derrangement with more ET-1 production in partial hepatectomy. In liver surgery, pharmacological regulation of ET-1 production may lead to attenuation of reperfusion injuries for ischemically damaged cirrhotic liver.