並列タイトル等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
一般注記type:Thesis
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.
博士(医学)・甲612号・平成26年3月17日
identifier:Hepatology research Vol.43 No.11 p.1241-1250
identifier:13866346
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2697
identifier:Hepatology research, 43(11): 1241-1250
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)
提供元機関・データベース奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU