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Development of Therapentic Method to Promote Liver Regeneration by Modulating the Activin-Follistatin System

通过调节激活素-卵泡抑素系统促进肝脏再生的治疗方法的开发

基本信息

批准号：
05557034
负责人：
KOJIMA Itaru
金额：
$ 10.56万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05557034/
关键词：
liver regeneration activin A follistatin growth factor hepatectomy hepatic necrosis growth DNA synthesis 肝壊死オートクリン機構

项目摘要

Activin A is an autocrine growth inhibitor of hepatocytes. When hepatocytes were stimulated by growth factors, activin A is synthesized in the middle to late G_1 phase and inhibits initiation of DNA synthesis. Reversal of the inhibitory effect of activin A by adding follitatin, an activin-binding protein, augments DNA synthesis. Activin A is expressed in the remnant liver after partial hepatectomy. When follistatin was infused into the rat portal vein immediately after the 70% hepatectomy, liver regeneration was accelerated. Initiation of DNA synthesis was observed 6 hrs earlier than in control rats. The remnant liver weight and liver regeneration rate were significantly greater in follistatin-treated rats. When ^<125>I-follistatin administered intravenously, about 10% of the ^<125>I-follistatin was accumulated in the liver. The amount of follistatin in the liver remained elevated for up to 72 hrs but decreased thereafter. A booster shot of follistatin at 72 hrs maintained the intrahepatic follistatin at the high level for up to 120 hrs. When follistatin was infused intravenously after 70% hepatectomy followed by a booster shot at 72 hrs, the liver regeneration, as assese by the DNA content, remnant liver weight and liver regeneration rate, was significantly augmented. These results indicate the effectiveness of follistatin in promoting liver regeneration after partial hepatectomy.

激活素A是肝细胞的自分泌生长抑制剂。当肝细胞被生长因子刺激时，激活素A在G_1中晚期合成，并抑制DNA合成的起始。通过添加卵泡素（一种激活素结合蛋白）来抑制激活素A的抑制作用，从而增强DNA合成。激活素A在部分肝切除术后的残肝中表达。在70%肝切除后立即将卵泡抑素注入大鼠门静脉，肝再生加速。DNA合成的起始比对照组大鼠早6小时。在卵泡抑素治疗的大鼠中，残余肝脏重量和肝再生率显著更大。当<125>静脉内给予β I-卵泡抑素时，约10%的β <125>I-卵泡抑素在肝脏中蓄积。肝脏中卵泡抑素的量在72小时内保持升高，但此后下降。在72小时的促滤泡素抑制素的加强注射使肝内促滤泡素抑制素维持在高水平长达120小时。当70%肝切除后静脉注射卵泡抑素，72小时后加强注射时，以DNA含量、残肝重量和肝再生率评估，肝再生明显增强。提示卵泡抑素对肝部分切除术后肝再生有促进作用。