The role of chymase in the disease preocess of non-alcoholic staetohepatitis (NASH)

食糜酶在非酒精性脂肪性肝炎（NASH）发病过程中的作用

• 批准号: 23591999
• 负责人: HAYASHI Michihiro
• 金额: $ 3.24万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591999/
• 关键词: キマーゼ; 非アルコール性脂肪性肝炎

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.

糜酶在血管紧张素II形成的增强中起作用，血管紧张素II参与肝纤维化。在MCDD诱导的仓鼠（H）NASH模型中研究了糜酶抑制剂（TY）的作用。开始TY或安慰剂治疗，并继续MCDD治疗12周。在12周后，在MCDD喂养的H中观察到肝脏脂肪变性和纤维化。肝脏中的MDA和胶原I、III、α-SMA和Rac-1的基因表达增加。在24周时，脂肪变性和纤维化在喂食MCDD的安慰剂治疗的H中更多，持续24周而不是12周。H在服用12周MCDD后服用TY 12周，脂肪变性和纤维化得到改善，与正常饮食喂养的H相比没有差异。在24周时，安慰剂治疗的H中AT II和MDA增加，胶原蛋白I、III、α-SMA和Rac-1表达增加;在TY治疗的H中这些降低至正常。TY不仅可以阻止肝脂肪变性和纤维化的进展，而且还可以改善它们。

项目成果

ハムスターNASHモデルに対するキマーゼ阻害薬の治療効果の検討

食糜酶抑制剂对仓鼠NASH模型的治疗作用考察

• 发表时间: 2012
• 作者: 鱒渕真介;髙井真司;金徳男;田代圭太郎;米田浩二;林道廣;内山和久
• 通讯作者: 内山和久

Chymase inhibitor ameliorates hepatic steatosis and fibrosis on established non-alcoholic steatohepatitis in hamsters fed a methionine- and choline-deficient diet

• DOI: 10.1111/hepr.12042
• 发表时间: 2013-09-01
• 期刊: HEPATOLOGY RESEARCH
• 影响因子: 4.2
• 作者: Masubuchi, Shinsuke;Takai, Shinji;Uchiyama, Kazuhisa
• 通讯作者: Uchiyama, Kazuhisa