2006 Fiscal Year Final Research Report Summary
Investigation for gene transfer regulation of organ failure induced by hepatic ischemia/reperfusion injury
| Project/Area Number |
17591371
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
YOSHIDOME Hiroyuki Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 講師 (10312935)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (70166156)
KIMURA Fumio Chiba University, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 助教授 (70334208)
KATO Atsushi Chiba University, Graduate School of Medicine, Assistant Professor, 医学部附属病院, 助手 (70344984)
YOSHITOMI Hideyuki Chiba University, Graduate School of Medicine, Assistant Professor, 医学部附属病院, 助手 (60375631)
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| Project Period (FY) |
2005 – 2006
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| Keywords | ischemia and reperfusion injury / transcriptional factor / infection / organ failure / cytokine / chemokine / sepsis / apoptosis |
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| Research Abstract |
Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation. One possible cause is hepatic ischemia/reperfusion. The aim of the current study was to determine the role for NOS isoform expression and apoptosis in steatotic liver ischemia/reperfusion injury. Using a murine model of partial hepatic ischemia, expression of NOS isoforms, apoptosis, transcriptional activation, serum ALT levels, and histology were examined. Although serum ALT levels were elevated and histology revealed severe liver injury in terms of steatosis relative to normal liver, steatotic ischemia/reperfusion injury was independent of neutrophil-mediated injury. In steatotic liver, an increase in iNOS expression but little upregulation of eNOS was evident and hepatic apoptosis defined by TUNEL staining was significantly induced which was associated with upregulation of cleaved caspases 9 and 3, but not caspase 8 compared with normal liver. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum ALT levels and apoptosis were greatly reduced, but treated with L-NAME, serum ALT levels were greatly upregulated in the steatosis compared with normal liver. Our data suggested that steatotic liver is vulnerable to ischemia/reperfusion which may be caused by different expression pattern of NOS isoforms and susceptibility to apoptosis by mitochondrial permeability transition.
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Research Products
(9 results)
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[Journal Article] Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy.2006
Author(s)
Makino H, Shimizu H, Ito H, Kimura F, Ambiru S, Togawa A, Ohtsuka M, Yoshidome H, Kato A, Yoshitomi H, Sawada S, Miyazaki M.
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Journal Title
World Journal of Gastroenterology 12
Pages: 2053-2059
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection.2006
Author(s)
Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Nozawa S, Furukawa K, Mitsuhashi N, Sawada S, Takeuchi D, Ambiru S, Miyazaki M.
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Journal Title
Journal of Surgical Research 133
Pages: 102-112
Description
「研究成果報告書概要(欧文)」より
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