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http://hdl.handle.net/10564/2697
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Title: | Direct renin inhibitor, aliskiren, attenuates the progression of non-alcoholic steatohepatitis in the rat model. |
Other Titles: | 直接的レニン阻害薬であるアリスキレンはラットモデルにおいて非アルコール性脂肪肝炎の進行を抑制する |
Authors: | Aihara, Yosuke Yoshiji, Hitoshi Noguchi, Ryuichi Kaji, Kosuke Namisaki, Tadashi Shirai, Yusaku Douhara, Akitoshi Moriya, Kei Kawaratani, Hideto Fukui, Hiroshi |
Keywords: | angiotensin-II hepatocarcinogenesis liver fibrosis non-alcoholic steatohepatitis renin |
Issue Date: | Nov-2013 |
Publisher: | Wiley / The Japan Society of Hepatology |
Citation: | Hepatology research Vol.43 No.11 p.1241-1250 |
Abstract: | AIM: Renin is a rate-limiting enzyme of the renin-angiotensin system (RAS), and
several reports have shown that renin plays an important role in several
pathological processes. Although RAS is known to play a pivotal role in the
progression of non-alcoholic steatohepatitis (NASH), the role of renin is still
obscure. The aim of the current study was to examine the effect of the clinically
used direct renin inhibitor (DRI), aliskiren, on the progression of NASH in a rat
model.
METHODS: The effects of DRI on the choline-deficient L-amino acid-defined (CDAA)
diet-induced rat NASH model was examined in conjunction with the activated
hepatic stellate cells (Ac-HSC) and neovascularization, both of which are known
to play important roles in liver fibrosis development and hepatocarcinogenesis,
respectively.
RESULTS: DRI exerted a marked inhibitory effect against liver fibrosis
development and glutathione-S-transferase placental form (GST-P) positive
preneoplastic lesions along with suppression of the Ac-HSC and neovascularization
in a dose-dependent manner. DRI also inhibited the hepatic expressions of
transforming growth factor-beta 1 (TGF-beta 1), angiotensin-II (AT-II) and
vascular endothelial growth factor (VEGF). These results indicated that renin
played a pivotal role in the liver fibrosis development and hepatocarcinogenesis
of NASH.
CONCLUSION: Because DRI is already widely used in the clinical practice with
safety, this drug may represent a potential new strategy against the progression
of NASH in the future. |
Description: | 博士(医学)・甲612号・平成26年3月17日 |
URI: | http://hdl.handle.net/10564/2697 |
ISSN: | 13866346 |
Academic Degrees and number: | 24601A612 |
Degree-granting date: | 2014-03-17 |
Degree name: | 博士(医学) |
Degree-granting institutions: | 奈良県立医科大学 |
Appears in Collections: | 2013年度
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