| Project/Area Number |
14570472
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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 |
Gastroenterology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
OCHI Koji OKAYAMA UNIVERSITY, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (60160884)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUSHIMA Takaaki OKAYAMA UNIVERSITY, University Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (20294407)
SHINJI Toshiyuki OKAYAMA UNIVERSITY, University Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (70314680)
KOIDE Norio OKAYAMA UNIVERSITY, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (20142333)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | free radicals / pancreas / fibrosis / chronic pancreatitis / stellate cell / 膵線進化 / SOD / PDGF / 経口蛋白分解酵素阻害剤 / 膵星細胞 / 肝星細胞 |
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| Research Abstract |
Pancreatic stellate cells (PSCs) have reported to play an important role on pancreatic fibrosis, which is implicated in pathophysiology of chronic pancreatitis. Alcohol abuse is a main etiological factor of chronic pancreatitis in developed countries including Japan. Although pancreatic fibrosis is associated with free radicals generated by metabolism of alcohol, exact mechanisms are still unknown. Therefore, we investigated how free radical act on PSC in vivo and in vitro, using an inhibitor of superoxide dismutase (SOD), DDC (diethldithiocarbamate). (1) We demonstrated that pancreatic fibrosis was induced and PSCs activated by repeated administrations of DDC, 500mg/kg BW for 2 weeks in rats. These changes were inhibited by a diet containing an oral trypsin inhibitor, camostat. (2) After cultured rat PSCs were incubated with DDC for 48 hours, SOD activity were decreased and lipid peroxidation products were increased in PSCs. In addition, DDC activated PSCs, increasing the number of α-smooth muscle (α-SMA) positive cells, enhancing secretion of collagen and matrix metalloproteinases, inhibiting PSCs proliferation in vivo. Secretion of tumor growth factor β (TGF-β), which is known to activate PSCs, was also increased by DDC in vivo. These alteration were prevented by addition of xanthine oxidase (XOD) inhibitor, allopurinol. There results suggested that free radicals generated by XOD might directly activate PSCs and induce pancreatic fibrosis.
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