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

内皮素1对硫代乙酰胺诱导肝硬化大鼠肝部分切除缺血/再灌注后微循环障碍的影响

• 批准号: 13671295
• 负责人: NAKAMURA Satoshi
• 金额: $ 1.15万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671295/
• 关键词: Endothelin-1; Liver cirrhosis; Hepatectomy; Microcirculation; Ischemia; Pringle's maneuver; Reperfusion injury; Time-resolved spectroscopy; エンドセリン; 再灌流傷害; 肝再生; 肝; 虚血; 再灌流

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.

内皮素 (ET)-1 会导致正常肝脏中的肝缺血和再灌注 (HIR) 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水平显着高于非肝硬化大鼠。间歇性肝缺血再灌注动物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，60-60岁末肝脏SO2下降与持续性肝缺血相比，微小肝缺血和再灌注后的肝缺血显着受到抑制。在连续肝缺血中使用非选择性内皮素受体拮抗剂进行预处理可显着改善血浆 AST 水平和肝脏 SO2 值，同时减少肝窦充血，从而提高 7 天生存率。肝硬化肝脏中的持续肝缺血具有与微循环紊乱相关的缺点，在部分肝切除术中会产生更多的 ET-1。在肝脏手术中，药物调节 ET-1 的产生可能会减轻缺血性损伤的肝硬化肝脏的再灌注损伤。

项目成果

Tsuchiya, Y., Suzuki, S., Inaba, K., Sakaguchi, T., Baba, S., Miwa, M., Konno, H., Nakamura, S.: "Impact of endothelin-1 on microcirculatory disturbance after partial hepatectomy under ischemia/reperfusion in thioacetamide-induced cirrhotic rats."J.Surg.R

Tsuchiya, Y.、Suzuki, S.、Inaba, K.、Sakaguchi, T.、Baba, S.、Miwa, M.、Konno, H.、Nakamura, S.：“内皮素 1 对微循环障碍的影响