A DEVELOPMENT OF THE NEW METHOD WHICH ACCELERATES LIVER REGENERATION BY USING PEPTIDE TECHNOLOGY

开发利用肽技术加速肝脏再生的新方法

• 批准号: 08557076
• 负责人: KOGURE Kimitaka
• 金额: $ 9.98万
• 依托单位: Gunma University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557076/
• 关键词: follistatin; activin A,; liver regeneration; hepatectomy; analog of follistatin; 90%肝切除

Augmentation of liver regeneration, with an artificial support to maintain liver function necessary for survival, would be beneficial for the treatment of fulminant hepatic failure caused by viral infection and hepatic toxins. As well, massive hepatectomy to resect liver tumors can be performed safely if the growth of the remnant liver is promoted effectively. Recently, the roles of various growth factors in the regulation of hepatocyte growth have been elucidated. Activin A which belongs to the transforming growth factor beta super gene family is a potent autocrine growth inhibitor in hepatocytes. Activin A is induced in vivo after partial hepatectomy. Low levels of the messenger RNA for the betaA-subunit of activin are markedly increased 20 hours after hepatectomy. When follistatin, which binds activin and blocks its action, is infused into the portal vein immediately after hepatectomy of 70%, DNA is synthesized several hours earlier than in control rats and liver regeneration is sig … More nificantly augmented. Follistatin provides a potential therapeutic approach to promoting liver regeneration because it specifically blocks autocrine growth inhibitor. The results were reported in Gastroenterology (vol 108 : 1136-1142,1195). Then, we obtained the results that the intravenous administration of follistatin effectively promoted liver regeneration after partial hepatectomy. These were reported in Hepatology (vol : 24 : 361-366,1996). We then investigated the effects of follistation on liver regeneration under more critical condition, 90% hepatectomy in rats and obtained the results that follistatin was quite effective in promothing liver regeneration. In this project we made four kinds of analog follistatin to select the amino acid sequence which were expected to express the effects of follistatin (1.heparin binding side, 2.3.follistatin module, 4.c-terminal), and made two types of follistatin which were constructed with 288 and 315 of amino acids. We are investigating the effects of these analog follistatins on liver regeneration. Less

肝脏再生的增强，并提供人工支持以维持生存所必需的肝功能，将有益于治疗由病毒感染和肝毒素引起的暴发性肝衰竭。同样，如果有效促进残余肝脏的生长，可以安全地进行大规模的肝术以恢复肝肿瘤。最近，已经阐明了各种生长因子在肝增长调节中的作用。属于转化生长因子β超基因家族的激活素A是肝细胞中潜在的自分泌生长抑制剂。部分肝术后体内诱导活化素A。肝切开术后20小时，用于β活化素β-亚基的信使RNA水平较低。当肝蛋白结合并阻断其作用的卵泡蛋白在肝术后立即感染到门静脉中时，与对照大鼠相比，DNA合成了几个小时，而肝脏再生则是SIG……更大程度地增强。 Follistatin提供了一种潜在的治疗方法来促进肝脏再生，因为它专门阻止了自分泌抑制剂。结果报道了胃肠病学（第108：1136-1142,1195卷）。然后，我们获得了结果，即肝静脉曲张素的静脉内给药可在部分肝切开术后有效促进肝脏再生。这些在肝病学中报道（第24卷：361-366，1996）。然后，我们调查了卵泡对肝脏再生的影响，在更为危急的情况下，大鼠的七十％的七十％，并获得了Follistatin在促进肝脏再生方面非常有效的结果。在这个项目中，我们制作了四种类似的类似物Follistatin，以选择氨基酸序列，这些氨基酸序列有望表达Follistatin（1.Heparin Binding Side，2.3.Follistatin模块，4.C末端）的作用，并制作了两种类型的Follistatin，这些模块由288和315构建为288和315氨基酸。我们正在研究这些类似物卵泡素对肝脏再生的影响。较少的

项目成果

Kimitaka Kogure, Masatoshi Ishizaki, Masaaki Nemoto, Masatoshi Makuuchi.: "Evaluation of serum uric acid changes in different forms of liver surgery." Journal of Hepato-Biliary-Pancreatic Surgery. 4. 45-45 (1997)

Kimitaka Kogure、Masatoshi Ishizaki、Masaaki Nemoto、Masatoshi Makuuchi.：“不同形式肝脏手术中血清尿酸变化的评估。”

Kimitaka Kogure, Waka Omata, Makoto Kanzaki, You-Quing Zhang, Hiroshi Yasuda, Tetsuya Mine, Itaru Kojima.: "A single intraportal administration of follistating accelerates liver regeneration in patrially hepatectomized rats." Gastroenterology. 108. 1136-1

Kimitaka Kogure、Waka Omata、Makoto Kanzaki、You-Quing Zhang、Hiroshi Yasuda、Tetsuya Mine、Itaru Kojima.：“单次门静脉内给予卵泡可加速父系肝切除大鼠的肝脏再生。”

Makoto Kanzaki: "Stimulation of follistatin production in cultured rats hepatocytes." Biochem.Biophys.Res.Commun.202. 422-428 (1994)

Makoto Kanzaki：“刺激培养大鼠肝细胞中卵泡抑素的产生。”

Kimitaka Kogure, Waka Omata, Makoto Kanzaki, Itaru Kojima.: "A stimulatory effect of follistatin of liver regeneration and the changes in biochemical markers after partial hepatectomy in rats." Final Program of 36th World Congress of Surgery. 215-215 (199

Kimitaka Kogure、Waka Omata、Makoto Kanzaki、Itaru Kojima.：“卵泡抑素对大鼠肝再生的刺激作用以及部分肝切除术后生化标志物的变化。”

Kimitaka Kogure, Y-Q Zhang, Makoto Kanzaki, Waka Omata, Itaru Kojima.: "Intravenous administration of follistatin ; Delivery to the liver and effect of liver regeneration." Abstract of 10th International Congress of Endocrinology. 825-825 (1996)

Kimitaka Kogure、Y-Q Zhang、Makoto Kanzaki、Waka Omata、Itaru Kojima.：“静脉注射卵泡抑素；递送至肝脏和肝再生效果。”