肝移植供肝缺血性损伤与再灌注损伤的比较蛋白质组学研究

吴斌; 武鸿莉; 陈建宁; 华学锋; 李宁; 陆敏强

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Proteomic analysis of human donor liver tissues subjected to ischemia/reperfusion injury during liver transplantation

首发时间：2013-03-27

WU Bin ¹
Wu Bin,（1972-），Man，Deputy chief physician，Clinical and basic research of liver transportation.
WU Hongli ² CHEN Jianning ³ HUA Xuefeng ¹ LI Ning ¹ LU Minqiang ¹
Lu Minqiang，Man，professor，clinical and basic research of liver transportation

1、Department of liver transplantation, the 3rd affiliated hospital of Sun-Yat-Sen University, Guangzhou 510630
2、Department of veterinary and biomedical sciences, 120 VBS, University of Nebraska-Lincoln, Lincon, USA, 68583-0905
3、Department of pathology, Tianhe road 600, The 3rd affiliated hospital of Sun-Yat- Sen University, Guangzhou, 510630

Abstract：Purpose: to explore the specific alterations in protein profiles that took place during ischemia/reperfusion injury (I/RI) and find novel therapeutic strategies to reduce I/RI during orthotopic liver transplantation (OLT). Method: we used the comparative proteomic approach of two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to compare the proteomic profiles of the same donor liver at three different time points: T1, immediately after cardiac arrest of donors (normal control). T2, before portal vein was recirculated (ischemia). T3, two hours after the anastomosis of the hepatic artery (reperfusion). Result: we identified 34 proteins that were significantly altered during I/RI. These differentially expressed proteins were functionally classified into seven categories: metabolic enzyme, molecular chaperone, antioxidant enzyme, cytoskeleton protein, signal transduction protein, cyclin, and binding protein. Among the 34 proteins, nine proteins changed only during ischemia (from T1 to T2) period, eleven proteins changed only during reperfusion (from T2 to T3) period, others changed during both ischemia and reperfusion (from T1 to T3) periods. Conclusion: ischemia and reperfusion during LT may lead to different modifications of the liver proteins. Most metabolic enzymes and antioxidant enzymes were up-regulated during ischemia period, indicated that lipidic metabolic disorder and oxidative stress were closely related to the development of ischemia injury. ER chaperones may play a vital role in mediating I/RI and prevention of ER stress caused by I/RI may be used as a key therapeutic target to improve the outcome of LT.

keywords： liver transportation ischemia reperfusion injury protemics

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肝移植供肝缺血性损伤与再灌注损伤的比较蛋白质组学研究

吴斌 ¹
Wu Bin,（1972-），Man，Deputy chief physician，Clinical and basic research of liver transportation.
武鸿莉 ² 陈建宁 ³ 华学锋 ⁴ 李宁 ⁴ 陆敏强 ⁴
Lu Minqiang，Man，professor，clinical and basic research of liver transportation

1、中山大学附属第三医院肝移植中心，广州 510630
2、内布拉加斯大学林肯分校氧化还原中心，美国 68583-0905
3、中山大学附属第三医院病理科，广州，510630
4、中山大学附属第三医院肝移植中心，广州，510630

摘要：目的：研究肝移植手术中供肝组织缺血-再灌注损伤的蛋白质变化规律并探讨减轻供肝缺血再灌注损伤的可能方法。方法：采用双向荧光差异凝胶电泳以及基质辅助激光解吸离子飞行质谱方法，对5例肝移植供肝于以下三个时间点切取肝组织标本进行蛋白质组学对照研究，①新鲜的供体肝组织。②经过缺血降温保存后修整完毕，但未经血管吻合的肝脏组织。③复流后的供肝组织。通过2DE-MALDI-TOF和质谱技术，对上述三个时间点的蛋白表达作出比较。结果：我们共发现与供肝缺血再灌注损伤有关的蛋白34个，按功能共分为代谢酶类、分子伴侣、氧化还原酶类等七类，在34种差异表达的蛋白中，9种蛋白仅在缺血期发生变化，11种蛋白质仅在再灌注损伤期发生变化，其余14种蛋白质在缺血性损伤期和再灌注损伤期均发生变化。结论：供肝缺血性损伤和再灌注损伤涉及的蛋白质种类不同，大多数代谢酶类和氧化还原酶类在供肝缺血期上调，提示脂质代谢和氧化应激与供肝缺血性损伤密切相关；内质网分子伴侣可能在调节供肝缺血再灌注损伤和防止内质网应激方面起到重要作用，因此有可能成为治疗供肝缺血再灌注损伤的靶点。

关键词：肝移植缺血再灌注损伤蛋白质组学

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WU Bin,WU Hongli,CHEN Jianning,et al. Proteomic analysis of human donor liver tissues subjected to ischemia/reperfusion injury during liver transplantation[EB/OL]. Beijing:Sciencepaper Online[2013-03-27]. https://www.paper.edu.cn/releasepaper/content/201303-898.

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论文编号	201303-898
论文题目	肝移植供肝缺血性损伤与再灌注损伤的比较蛋白质组学研究
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