Rho-kinase inhibitor targeting the liver prevents liver fibrosis without major systemic adversity in rats

2015 Fiscal Year Final Research Report

• Project/Area Number: 26861078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hiroshima University
• Principal Investigator: Shintaro Kuroda 広島大学, 大学病院, 医科診療医 (30457246)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 肝線維化 / 星細胞 / リポソーム / DDS / Rhoキナーゼ阻害剤

Outline of Final Research Achievements

Rho-kinase (ROCK) inhibitors improve liver blood flow after ischemia/reperfusion (IR) injury or improve liver fibrosis, by preventing the activation of hepatic stellate cell (HSC). However, the systemic administration of ROCK inhibitors causes severe hypotension; therefore, liver-specific ROCK inhibition is required. Here, we tested vitamin A coupled liposomes carrying the ROCK inhibitor for targeted HSCs in rat IR model and liver fibrosis model. Liposomal ROCK inhibitor was 100-fold more effective in inhibiting HSC activation than free ROCK inhibitor without major systemic adversity in rats.

Free Research Field

消化器外科