Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model

作     者：Friedrich Duenschede Kirsten Erbes Nina Riegler Patrick Ewald Achim Kircher Stefanie Westermann Arno Schad Imke Miesmer Simon Albrecht-Schck Ines Gockel Alexandra K Kiemer Theodor Junginger 

作者机构：Department of General and Abdominal Surgery University hospital Mainz Langenbeckstr.1 D-55131 Mainz Germany Institute for Pathology University hospital Mainz Germany Department of Pharmacy Pharmaceutical Biology Saarland University 66123 Saarbrücken Germany 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2007年第13卷第27期

页      面：3692-3698页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Warm liver ischemia Liver preconditioning Apoptosis Lipid peroxidation Pharmacological preconditioning 

摘      要：AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning （IP） as well as pharmacologic pretreatment by α-lipoic acid （LA）. METHODS： Several groups of rats were compared： sham operated animals, non-pretreated animals （nt）, animals receiving IP （10 rain of ischemia by clamping of the portal triad and 10 min of reperfusion） prior to sustained ischemia, animals receiving selective ischemic preconditioning （IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 rain of reperfusion） prior to sustained ichemia, and animals receiving 500 1μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS： Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA（19 ± 2 vs 10 ± 1, P〈 0.05 and 29 ± 5 vs 12 ± 1, P 〈 0.05）. Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment （3.1 ± 0.3 vs 1.8 ± 0.2, P 〈 0.05）. Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation （LPO） in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION： IP, consisting of 10 min of ischemia and 10 min of reperfusion, ischemia/reperfusion injury protects only partly against of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.