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.

活化素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，在G_1期间至后期合成了激活素A并抑制DNA合成的启动。通过添加follitatin（一种激活蛋白结合蛋白）增强DNA合成来逆转激活素A的抑制作用。部分肝切除术后在残留肝脏中表达活化素A。 70％肝切除术后立即将卵泡蛋白立即注入大鼠门静脉时，肝脏再生加速。比对照大鼠早6小时观察到DNA合成的起始。在经卵泡蛋白治疗的大鼠中，残留的肝脏体重和肝脏再生率明显更高。当 ^<125> i-follistatin静脉内给药时，大约10％的 ^<125> i-follistatin积聚在肝脏中。肝脏中的卵泡素数量保持高达72小时，但此后减少。 72小时的Follistatin的助推器射击使肝内的卵泡素保持高水平长达120小时。 70％的肝切除术后将卵泡素静脉注射，然后在72小时的助球射击时，肝脏再生，作为DNA含量，残留肝脏重量和肝脏再生率的囊肿，大大增加了。这些结果表明，卵泡素在部分肝切除术后促进肝脏再生方面的有效性。