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缺血性与药物性肝预处理

Ischemic versus pharmacologic hepatic preconditioning.

作者信息

Balzan Silvio Marcio Pegoraro, Gava Vinicius Grando, Rieger Alexandre, Pra Daniel, Trombini Luciano, Zenkner Fernanda Fleig, Horta Jorge André, Azambuja Guaraci, Schopf Luciano, de Souza Pedro Lucio

机构信息

Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Department of Surgery, Moinhos de Vento Hospital, Porto Alegre, Brazil.

Department of Biology and Pharmacy, School of Medicine, University of Santa Cruz do Sul (UNISC), Santa Cruz do Sul, Brazil; Department of Surgery, Moinhos de Vento Hospital, Porto Alegre, Brazil.

出版信息

J Surg Res. 2014 Sep;191(1):134-9. doi: 10.1016/j.jss.2014.03.073. Epub 2014 Apr 1.

Abstract

BACKGROUND

Hepatic ischemia-reperfusion injury has a significant impact on liver resection and transplantation. Many strategies have been developed to reduce the effects of ischemia-reperfusion injury, including pharmacologic and ischemic preconditioning; however, studies comparing these two methods are lacking.

MATERIAL AND METHODS

An experimental study was performed in a swine model. Eighteen swine were randomly assigned to three different groups: an ischemic preconditioning (IschPC) group, a pharmacologic preconditioning (PharmPC) group, and a control group. All animals underwent a 40-min liver ischemia, followed by 40 min of reperfusion. The IschPC group received a short period of ischemia (10 min) and a short period of reperfusion (15 min) before prolonged ischemia. The PharmPC group received inhaled sevoflurane for 30 min before prolonged ischemia. The control group did not receive any intervention before prolonged ischemia. Blood samples and liver tissue were obtained after ischemic and reperfusion periods. Injury was evaluated by measure of DNA damage (using COMET assay) and serum biochemical markers (transaminases, alkaline phosphatase, amylase, bilirubin, and C-reactive protein [CRP]).

RESULTS

No significant difference was found in serum biochemical markers, except for the C-reactive protein level that was lower in the PharmPC group than in the control group soon after hepatic ischemia. Soon after prolonged ischemia, DNA damage index, both in blood samples and in liver tissue samples, was similar among the groups. However, an increase in DNA damage after reperfusion was higher in the control group than in the PharmPC group (P < 0.05). The increase in DNA damage in the IschPC group was half of that observed in the control, but this difference was not statistically significant.

CONCLUSIONS

Our results suggest an early protective effect of PharmPC (lower levels of C-reactive protein soon after ischemia). The protective effect observed after reperfusion was higher with PharmPC than with ischemic preconditioning. The simultaneous use of both methods could potentiate protection for ischemia-reperfusion.

摘要

背景

肝缺血再灌注损伤对肝切除和肝移植有重大影响。已开发出多种策略来减轻缺血再灌注损伤的影响,包括药物预处理和缺血预处理;然而,比较这两种方法的研究尚缺乏。

材料与方法

在猪模型上进行了一项实验研究。18只猪被随机分为三组:缺血预处理(IschPC)组、药物预处理(PharmPC)组和对照组。所有动物均经历40分钟的肝脏缺血,随后再灌注40分钟。IschPC组在长时间缺血前接受短时间缺血(10分钟)和短时间再灌注(15分钟)。PharmPC组在长时间缺血前吸入七氟醚30分钟。对照组在长时间缺血前未接受任何干预。在缺血和再灌注期后采集血样和肝组织。通过测量DNA损伤(使用彗星试验)和血清生化标志物(转氨酶、碱性磷酸酶、淀粉酶、胆红素和C反应蛋白[CRP])来评估损伤。

结果

血清生化标志物无显著差异,除了肝缺血后不久PharmPC组的C反应蛋白水平低于对照组。长时间缺血后不久,血样和肝组织样本中的DNA损伤指数在各组间相似。然而,再灌注后对照组的DNA损伤增加高于PharmPC组(P<0.05)。IschPC组的DNA损伤增加是对照组观察到的一半,但这种差异无统计学意义。

结论

我们的结果表明药物预处理具有早期保护作用(缺血后不久C反应蛋白水平较低)。再灌注后观察到的保护作用,药物预处理高于缺血预处理。两种方法同时使用可增强对缺血再灌注的保护作用。

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