| Co-Investigator(Kenkyū-buntansha) |
TOGO Shinji Yokohama City University, Graduate School of Medicine, Medical Research Department, Assistant Professor, 大学院・医学研究科, 助教授 (10244477)
HAYASHIZAKI Yoshihide RIKEN Genomic Science Center, Laboratory for Genome Exploration Research Group, Research Director, ゲノム科学総合研究センター, 研究職 (70192705)
岡崎 康司 理化学研究所, ゲノム科学総合研究センター, 研究職チームリーダー (80280733)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
[Background] In the medical treatment of a liver malignant tumor, in order to increase the amount of permission hepatectomy and to obtain improvement in the rate of recovery excision, control of postoperative hepatic insufficiency, as a result a prognostic improvement, it is important to solve the hepatic insufficiency mechanism after excessive hepatectomy, and to develop the measure. 70% hepatectomized mice are established as a liver regeneration model, it is applied to a knockout mouse, and the research for the mechanism of liver regeneration is made. However, since it is difficult in technique, the fatality hepatectomy model is not established in the mouse. [Aim] We developed the mouse 90% hepatectomy model as an excessive hepatectomy model this time using C57BL/6J male eight-week old mouse. Furthermore, in order to clarify mechanism on gene of the hepatic insufficiency after hepatectomy, and the mechanism of liver reproduction and to develop the measure against prevention of the he
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patic insufficiency after excessive hepatectomy. We analyzed gene expression profiles between 90% hepatectomized mice as an excessive hepatectomy model and 70% hepatectomized mice as a liver regeneration model using cDNA microarray. [Result] The 90%-hepatectomized mice all died within 24 hours after hepatectomy. We established 70% hepatectomy as the safety limit for murine hepatectomy and as a model far liver regeneration, and 90% hepatectomy as a "fatal hepatic failure level". And in cDNA microarray, gene expression patterns differed, in the both models, low discovery of the gene cluster relevant to liver reproduction was accepted 90%, the obstacle of a sugar metabolic pathway was accepted especially among metabolic pathwaies, and both models were further considered that control has arisen in the reproduction mechanism. The down-regulated genes in 90% partial hepatectomized mice after hepatectomy were liver regeneration related genes and glucose metabolism related genes. We concluded that fatal hepatic failure after excessive hepatectomy was characterized by arrest of cell cycle. Among the gene clusters extracted by cDNA microarray, about some things, the same result was obtained also by RT-PCR and the reliability of this examination using cDNA microarray was checked. Furthermore, about details, it is under examination now. Moreover, we developed the hepatectomy model using the knockout mouse of TNF-alpha receptor and IL-6 receptor which is that of a factor important for liver reproduction. it checked that delay of liver reproduction is accepted as compared with a normal mouse, gene discovery analysis is performed using cDNA microarray, and the gene cluster related to delay of liver reproduction is under examination. [Future view] Detailed gene discovery analysis by cDNA microarray is due to be performed using a knockout mouse. Less
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