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。

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