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), andseveral reports have shown that renin plays an important role in severalpathological processes. Although RAS is known to play a pivotal role in theprogression of non-alcoholic steatohepatitis (NASH), the role of renin is stillobscure. The aim of the current study was to examine the effect of the clinicallyused direct renin inhibitor (DRI), aliskiren, on the progression of NASH in a ratmodel.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 activatedhepatic stellate cells (Ac-HSC) and neovascularization, both of which are knownto play important roles in liver fibrosis development and hepatocarcinogenesis,respectively.RESULTS: DRI exerted a marked inhibitory effect against liver fibrosisdevelopment and glutathione-S-transferase placental form (GST-P) positivepreneoplastic lesions along with suppression of the Ac-HSC and neovascularizationin a dose-dependent manner. DRI also inhibited the hepatic expressions oftransforming growth factor-beta 1 (TGF-beta 1), angiotensin-II (AT-II) andvascular endothelial growth factor (VEGF). These results indicated that reninplayed a pivotal role in the liver fibrosis development and hepatocarcinogenesisof NASH.CONCLUSION: Because DRI is already widely used in the clinical practice withsafety, this drug may represent a potential new strategy against the progressionof 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
DOIinfo:doi/10.1111/hepr.12081
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