在大鼠模型中，缺血预处理及在肝脏缺血90分钟前应用硫辛酸的保护作用。
Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model.
作者信息
Duenschede Friedrich, Erbes Kirsten, Riegler Nina, Ewald Patrick, Kircher Achim, Westermann Stefanie, Schad Arno, Miesmer Imke, Albrecht-Schöck Simon, Gockel Ines, Kiemer Alexandra K, Junginger Theodor
机构信息
University Hospital Mainz, Department of General and Abdominal Surgery, Langenbeckstrasse 1, 55131 Mainz, Germany.
出版信息
World J Gastroenterol. 2007 Jul 21;13(27):3692-8. doi: 10.3748/wjg.v13.i27.3692.
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 alpha-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 ischemia, and animals receiving 500 micromol alpha-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 apoptotic 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.
目的
比较不同预处理策略对肝脏缺血/再灌注损伤的保护作用，重点关注促凋亡蛋白和抗凋亡蛋白的表达。干预措施包括不同模式的缺血预处理（IP）以及α-硫辛酸（LA）的药物预处理。
方法
比较了几组大鼠：假手术动物、未预处理动物（nt）、在持续缺血前接受IP（通过夹闭门静脉三联10分钟缺血和10分钟再灌注）的动物、在持续缺血前接受选择性缺血预处理（IPsel，通过选择性夹闭缺血叶10分钟缺血和10分钟再灌注）的动物，以及在诱导90分钟选择性缺血前15分钟静脉注射500微摩尔α-LA的动物。
结果
仅LA组细胞损伤减少。TUNEL阳性肝细胞以及坏死性肝细胞损伤也仅通过LA减少（19±2对10±1，P<0.05；29±5对12±1，P<0.05）。肝脏组织中caspase 3活性未改变，仅LA预处理使肝脏组织中caspase 9活性降低（3.1±0.3对1.8±0.2，P<0.05）。作为肝功能终点的生存率在IP和LA预处理后升高，但IPsel预处理后未升高。与nt组相比，IP组和LA组肝脏组织中的脂质过氧化（LPO）水平降低。促凋亡蛋白和抗凋亡蛋白的测定显示LA使抗凋亡蛋白增加。相比之下，我们的两种IP策略均未能影响凋亡性细胞死亡。
结论
由10分钟缺血和10分钟再灌注组成的IP仅部分保护肝脏在90分钟选择性缺血前免受缺血/再灌注损伤。IPsel不影响肝脏的缺血耐受性。LA可能通过下调促凋亡的Bax改善对缺血的耐受性。
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