2013 Fiscal Year Final Research Report
The role of chymase in the disease preocess of non-alcoholic staetohepatitis (NASH)
| Project/Area Number |
23591999
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKAI Shinji 大阪医科大学, 医学部, 准教授 (80288703)
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| Project Period (FY) |
2011 – 2013
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| Keywords | キマーゼ / 非アルコール性脂肪性肝炎 |
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| Research Abstract |
Chymase plays a role in the augmentation of angiotensin II formation,which is involved in liver fibrosis. The effects of a chymase inhibitor (TY), were investigated in MCDD-induced Hamsters (H) NASH model. Treatment with TY or placebo was initiated, and continued with MCDD for other 12 weeks. At 12 weeks after, hepatic steatosis and fibrosis were observed in MCDD-fed H.MDA and gene expression of collagen I, III,alpha-SMA and Rac-1 in liver were increased. At 24 weeks, steatosis and fibrosis were more in the placebo-treated H fed MCDD for 24 weeks vs.12 weeks. H treated with TY for 12 weeks after being on a 12-week MCDD had ameliorations in steatosis and fibrosis, with no differences compared to normal diet-fed H. There were augmentations in AT II and MDA, and expression of collagen-I, III,alpha-SMA and Rac-1 in the placebo-treated H at 24 weeks; these were reduced to normal in TY-treated H. TY not only prevented the progression of hepatic steatosis and fibrosis, also ameliorated them.
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