reventive and ameliorative effects of chymase inhibitor and MMP inhibitor on sinusoidal obstruction syndrome

• Project/Area Number: 26462049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka Medical College
• Principal Investigator: KOMEDA Koji 大阪医科大学, 医学部, 非常勤講師 (70531896)
• Co-Investigator(Kenkyū-buntansha): 高井 真司 大阪医科大学, 医学研究科, 教授 (80288703)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: キマーゼ / ＭＭＰ / 肝類洞閉塞症候 / 阻害薬 / 予防 / 治療 / マトリックスメタロプロテアーゼ / モノクロタリン / 酸化ストレス / 肝細胞壊死 / 肥満細胞 / TNF-α

Outline of Final Research Achievements

The effects of chymase inhibitor and matrix metalloproteinase (MMP) inhibitor were evaluated in monocrotaline-induced sinusoidal obstruction syndrome (SOS) mice. Both hepatic chymase activity and MMP-9 level were significantly augmented 2 days after monocrotaline administration. Significant increases of plasma AST and ALT were significantly decreased by chymase and MMP inhibitors, and the ratio of hepatic necrotic area was also significantly attenuated. Chymase-dependent MMP-9 augmentation was involved in the development of SOS, and chymase and MMP inhibitors were useful for prevention of the development of SOS.