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

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World Journal of Gastroenterology 2007年第27期13卷 3692-3698页

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 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

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 min 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 min of reperfusion) prior to sustained ichemia, and animals receiving 500 μmol 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 towardsanti-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, protects only partly against ischemia/reperfusion injury 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.

关键词：肝缺血肝预处理脂质过氧化反应药理学预处理预处理策略

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