Pathophysiological study of lower limb ischemia-reperfusion injury for development new drug therapy

• Project/Area Number: 23792078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: NAHO Kato 福島県立医科大学, 医学部, 助教 (20457766)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 虚血再還流障害 / 挫滅症候群 / IL-6ノックアウトマウス / iNOSノックアウトマウス / シベレスタット / エダラボン / IL-6 / iNOS / GM-CSF / 虚血再還流

Outline of Final Research Achievements

The mouse bilateral hind limb tourniquet-reperfusion model can be considered as an experimental animal model of crush syndrome. By using this model, we investigated mRNA expression levels of various inflammatory cytokines in the lung, liver and kidney. We were administered sivelestat (Siv), edaravone (Ed) or saline intraperitoneally into mice, at the various timings. In the result, we found that the TNF-a was reduced by Siv administration, and the suppression of iNOS　was reduced by Ed administration in kidney. IL-6 expression level was remained static by any drugs. Summed up that the results of survival assay in IL-6 KO and iNOS KO mice, blood concentration of inflammatory cytokines, oxidative stress and antioxidative potency, it was emerged the factors of reduce I/R injury that induction of IL-6 expression, stability of NO synthesis ability, decreased blood levels of TNF-a, IL-1a and IL-1b. We tried cross IL-6 and iNOS double KO mice, but drought in birth within a time frame.

Research Products

• [Journal Article] Interleukin-6 modulates oxidative stress produced during the development of cisplatin nephrotoxicity (2013)
  • Author(s): S Mitazaki, M Hashimoto, Y Matsuhashi, S Honma, M Suto, N Kato, O Nakagawasai, K Tan-No, K Hiraiwa, M Yoshida, S Abe
  • Journal Title: Life Sciences Volume: 92 Issue: 12 Pages: 694-700
  • DOI: 10.1016/j.lfs.2013.01.026
  • Peer Reviewed
• [Presentation] 緊縛性ショックにおけるエダラボンの効果について (2015)
  • Author(s): 加藤菜穂
  • Organizer: 第99次日本法医学会学術全国集会
  • Place of Presentation: 高知
  • Year and Date: 2015-06-11
• [Presentation] 緊縛性ショックモデルマウスにおけるシベレスタットの効果 (2011)
  • Author(s): 加藤菜穂
  • Organizer: 第12回日本法医学会学術北日本地方集会
  • Place of Presentation: 弘前
• [Presentation] 緊縛性ショックモデルマウスの血中サイトカイン濃度とシベレスタットの効果
  • Author(s): 加藤菜穂
  • Organizer: 第96次日本法医学会学術全国集会
  • Place of Presentation: 浜松