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

内皮素(ET)-1参与正常肝脏缺血再灌注损伤。本研究旨在阐明ET-1在肝硬化HIR损伤中的作用。肝硬化大鼠肝脏ET-1水平明显高于非肝硬化大鼠。与连续肝缺血动物相比，间歇肝缺血动物再灌注1、3、6小时血浆和肝脏ET-1水平，再灌注1、3、6小时血浆AST水平升高，缺血60分钟末和再灌注后肝脏SO2下降明显受到抑制。非选择性内皮素受体拮抗剂预处理持续肝缺血可显著改善血浆AST水平和肝脏SO2值，减少肝窦充血，从而提高7天生存率。肝硬化持续肝缺血在部分肝切除术中有微循环紊乱和更多ET-1产生的缺点。在肝脏手术中，对ET-1产生的药理调节可能导致肝硬化缺血性损伤肝脏再灌注损伤的减弱。

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.