2019年6月
Vitamin A-coupled liposomal Rho-kinase inhibitor ameliorates liver fibrosis without systemic adverse effects
HEPATOLOGY RESEARCH
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- 巻
- 49
- 号
- 6
- 開始ページ
- 663
- 終了ページ
- 675
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/hepr.13317
- 出版者・発行元
- WILEY
Aim Rho-kinase (ROCK) inhibitor could ameliorate liver fibrosis by suppressing hepatic stellate cell (HSC) activation. However, because systemic administration of ROCK inhibitor causes serious adverse effects, we developed a drug delivery system selectively delivering ROCK inhibitor to HSCs. Here, we examined whether our developed vitamin A (VA)-coupled liposomal ROCK inhibitor reduced liver fibrosis in rats without causing systemic adverse effects. Methods LX-2 HSCs were analyzed for morphological changes and the expression of profibrotic proteins. The inhibitory effects of VA-coupled liposomal ROCK inhibitor on liver fibrosis were confirmed in a rat model of liver fibrosis induced by i.p. injection of carbon tetrachloride. The degree of liver fibrosis, biochemical changes, and survival rates were also investigated. Results Vitamin A-coupled liposomal ROCK inhibitor had an effect at approximately 1/100 the amount of the free ROCK inhibitor for inhibiting the activation of LX-2 cells and caused significant decreases in the expression levels of alpha-smooth muscle actin (SMA) and transforming growth factor (TGF)-beta 1. The degree of liver fibrosis was suppressed by treatment with V
- リンク情報
- ID情報
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- DOI : 10.1111/hepr.13317
- ISSN : 1386-6346