Therapeutic approach against surgical injury of diseased liver : Proteomics approach

针对病变肝脏手术损伤的治疗方法：蛋白质组学方法

• 批准号: 18591528
• 负责人: NAKANO Hiroshi
• 金额: $ 2.49万
• 依托单位: St.Marianna University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591528/
• 关键词: Steatohepatitis; Zucker rat; Ischemic preconditioning; Ischemia reperfusion; Proteomics; Mitochoindrial protein; 脂肪肝; homozygous Zucker rat; mitochondria; proteomics; ischemic preconditioning; ischemia reperfusion injury; ミトコンドリア蛋白; プロテオミクス /

Background/Aim: Steatohepatitis has been shown to be vulnerable to surgical injury. Ischemic preconditioning (IPC) has been shown to reduce hepatic ischemia-reperfusion (IR) injury of steatotic liver, but the effect of IPC on mitochondrial proteome has not been fully demonstrated. The present study investigated how IPC modifies the mitochondrial proteome after IR injury of the rat steatohepatitis model.Methods: Zucker steatotic rats fed a choline-methionine deficient diet, and resulted in steatohepatitis model. These rats were subjected to 30-min of 70% hepatic iscemia (IR group). In the IPC group, 10-min temporal clamping followed by 1.0-min reperfusion was performed before the 30-min of the 70% hepatic clamping. Mitochondrial proteome was analyzed 24 hours after IR using two-dimensional differential in-gel electrophoresis and mass spectrometry.Results : Mitochondrial inner-membrane potential and glutathione were significantly maintained in the IPC group compared to the IR group. There was a greater degree of up-regulation of the mitochondrial precursor of aldehyde dehydrogenase 2, alpha-methylacyl-CoA racemase, carbonic anhydrase 3, and Mn-superoxide dismutase in the IPC group compared to those in the IR group.Conclusions : A hepato-protective effect was shown by IPC in steatohepatitis rats

背景/目的：脂肪性肝炎已被证明易受手术损伤。缺血预处理（IPC）可减轻脂肪肝肝缺血再灌注（IR）损伤，但IPC对线粒体蛋白质组的影响尚未完全阐明。本研究探讨IPC如何改变大鼠脂肪性肝炎模型IR损伤后的线粒体蛋白质组。方法：Zucker脂肪大鼠喂养胆碱-蛋氨酸缺乏的饮食，造成脂肪性肝炎模型。这些大鼠受到30分钟的70%肝缺血（IR组）。IPC组在70%肝钳夹30 min前先行颞叶钳夹10 min再灌注1.0 min。线粒体蛋白质组分析24小时后，IR使用二维差示凝胶电泳和质谱。结果：线粒体内膜电位和谷胱甘肽在IPC组相比，IR组显着维持。与IR组相比，IPC组大鼠肝组织线粒体乙醛脱氢酶2前体酶、α-甲基酰辅酶A消旋酶、碳酸酐酶3和锰超氧化物歧化酶表达上调程度更大。结论：IPC对脂肪性肝炎大鼠具有保护作用

项目成果

Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy

• DOI: 10.1097/sla.0b013e31815774de
• 发表时间: 2008-01-01
• 期刊: ANNALS OF SURGERY
• 影响因子: 9
• 作者: Nakano, Hiroshi;Oussoultzoglou, Elie;Jaeck, Daniel
• 通讯作者: Jaeck, Daniel

Modification of the Hepatic Mito-chondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver.

大鼠肝脏缺血再灌注损伤后肝脏线粒体蛋白质组的修饰对缺血预处理的反应。

• 发表时间: 2008
• 期刊: Eur Surg Res. 40
• 作者: Oshima R;Nakano H;Katayama M;Sakurai J;Wu W;Koizumi S;Asano T;Watanabe T;Asakura T;Ohta T;Otsubo T
• 通讯作者: Otsubo T

Blue liver syndrome increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Mumbai, India

蓝肝综合征会增加接受术前化疗的结直肠肝转移患者主要肝切除术后的发病率。

• 发表时间: 2008
• 作者: Nakano H;et. al.
• 通讯作者: et. al.

The Role of the New Ca2+ Antagonist, CV159, in Hepatic I/R Injury-The Evaluation of Hepatic Organ Reducing Activity Using In Vivo and Ex Vivo EPR.

新型 Ca2 拮抗剂 CV159 在肝 I/R 损伤中的作用 - 使用体内和离体 EPR 评估肝器官还原活性。

• 发表时间: 2008
• 期刊: Journal of Surgical Research 145
• 作者: Taiji Watanabe;Shigeru Oowada;Hiromichi P. Kobayashi;Masato Kamibayashi;Atsuko Ishiuchi;Yuji Jinnouchi;Satoshi Koizumi;Takayuki Asano;Tsukasa Shimamura;Takeshi Asakura;Hiroshi Nakano;Sunao Kubota;Takehito Otsubo.
• 通讯作者: Takehito Otsubo.

Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning Following Ischemia-Reperfusion Injury of the Rat Steatotic Liver.Eur Surg Res (in press)

大鼠脂肪肝缺血再灌注损伤后肝线粒体蛋白质组的修饰对缺血预处理的反应。Eur Surg Res（印刷中）

• 发表时间: 2008
• 期刊: Eur Surg Res 40(3)
• 作者: Oshima R;et. al.
• 通讯作者: et. al.