Exploitation of a novel therapy for fulminant hepatitis using microbubbles for contrast enhancement ultrasound

• Project/Area Number: 26460991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Toyama
• Principal Investigator: Minemura Masami 富山大学, 附属病院, 講師 (10313602)
• Co-Investigator(Kenkyū-buntansha): 杉山 敏郎 富山大学, 大学院医学薬学研究部(医学), 教授 (00196768)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 劇症肝炎 / 肝マクロファージ / 超音波造影剤 / マクロファージ / マイクロバブル / 腸内細菌

Outline of Final Research Achievements

To clarify the importance of liver macrophages (Kupffer cells) in pathogenesis of fulminant hepatitis and to find a new therapeutic approach, we used a mouse fulminant hepatitis model induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS) and visualized dynamics of liver macrophages　using contrast enhanced ultrasonography with microbubble-based contrast agent (Sonazoid). We compared the changes of Sonazoid-enhanced echogenicity with the histological distribution of macrophages. While the number of liver macrophages was extremely increased in the fulminant hepatitis group compared to the control group, the echogenicity in Kupffer-phase image was slightly increased in the fulminant hepatitis group. This study shows the possibility that the microbubble agent is a non-invasive useful tool for detecting dynamics of macrophages during acute liver injury, but the consideration is needed for changes of liver blood flow and macrophage phagocytic activity at the same time.

Research Products

• [Presentation] マクロファージと細菌の相互作用の検討 (2016)
  • Author(s): 峯村正実，田尻和人，河合健吾，高木宏明，安村敏，高原照美，杉山敏郎
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 東京ベイ幕張ホール（千葉市）
  • Year and Date: 2016-05-19
• [Presentation] Analysis of the Direct Interaction between Macrophages and Microbiota (2016)
  • Author(s): Masami Minemura, Yasuhiro Nakayama, Katsuharu Hirano, Yoshiharu Tokimitsu, Kazuto Tajiri, Kengo Kawai, Hiroshi Kudo, Yutaka Yata, Satoshi Yasumura, Terumi Takahara, and Toshiro Sugiyama
  • Organizer: 25th Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-02-22
  • Int'l Joint Research