The gene therapy for sepsis by the clarification of STAT3 / SOCS3 which control an inflammatory or an anti-inflammatory reaction

2016 Fiscal Year Annual Research Report

• Project/Area Number: 25462809
• Research Institution: Hokkaido University
• Principal Investigator: 澤村 淳 北海道大学, 医学研究科, 准教授 (00241448)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 外傷 / 敗血症 / DIC / 臓器不全

Outline of Annual Research Achievements

①IL-6 KOマウス（以下IL-M）、Wild Typeマウス（以下WT-M）の各30匹にLPS投与し致死率はIL-Mが46.7%に対し、WT-Mは96.7%であった。平均生存期間はIL-Mは 3.82日、WT-Mは2.26日であった。
②TNF-αKOマウス（以下TNF-M）とWT-Mの各25匹にLPS投与し致死率はTNF-Mが32.0%、WT-Mは100.0%であった。平均生存期間はTNF-Mが3.38日、WT-Mは2.44日であった。
③IL-Mを用いてRT-PCRを行った。Ct値はIL-MのLPS投与群でSOCS3（以下SO-3）が27.8、STAT3（以下ST-3）が19.9、WT-MはSO-3が25.2、ST-3が18.3であった。また、LPS非投与群ではIL-MはSO-3が29.9、ST-3が20.4でありWT-MはSO-3が27.8、ST-3が20.0であった。つまり、IL-MではSO-3の増幅効率がST-3に比べ高値であった。しかも、LPS投与群では非投与群に比べSO-3とST-3の増幅効率が共に抑制された。
④TNF-Mを用いたRT-PCRを行った。Ct値はTNF-MのLPS投与群でSO-3が27.5、ST-3が13.6でありWT-MはSO-3が25.6、ST-3が18.3であった。また、LPS非投与群ではTNF-MのSO-3が30.5、ST-3が18.4でありWT-MはSO-3が30.4、ST-3が14.2であった。つまり、TNF-MではLPS投与群でST-3の増幅効率がSO-3にくらべ明らかに抑制された。しかも、LPS非投与群ではST-3の増幅効率がWT-Mに比べTNF-Mで高値であった。
⑤以上から敗血症病態の進展にIL-6, TNF-αの関与つまりST-3の17q21.31とSO-3の17q25.3の遺伝子が関連しているものと考えられた。

Research Products

• [Journal Article] Activated protein C does not increase in the early phase of trauma with disseminated intravascular coagulation: comparison with acute coagulopathy of trauma-shock. (2016)
  • Author(s): Jesmin S, Gando S, Wada T, Hayakawa M, Sawamura A
  • Journal Title: Journal of Intensive Care Volume: 4 Pages: 1
  • DOI: DOI: 10.1186/s40560-015-0123-2
  • Peer Reviewed / Open Access
• [Journal Article] Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest. (2016)
  • Author(s): Wada T, Gando S, Ono Y, Maekawa K, Katabami K, Hayakawa M, Sawamura A
  • Journal Title: Thrombosis Journal Volume: 14 Pages: 43
  • DOI: 10.1186/s12959-016-0116-y
  • Peer Reviewed / Open Access
• [Journal Article] The response time threshold for predicting favourable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest. (2016)
  • Author(s): Ono Y, Hayakawa M, Iijima H, Maekawa K, Kodate A, Sadamoto Y, Mizugaki A, Murakami H, Katabami K, Sawamura A, Gando S
  • Journal Title: Resuscitation Volume: 107 Pages: 65-70
  • DOI: 10.1016/j.resuscitation.2016.08.005
  • Peer Reviewed / Open Access
• [Presentation] DIC and fibrinolysis in patients with trauma and out-of-hospital cardiac arbest. (2016)
  • Author(s): Gando S, Wada T, Ono Y, Maekawa K, Katabami K, Hayakawa M, Sawamura A.
  • Organizer: The 9th Congress of Asian-Pacific Society on Thrombosis and Hemostasis
  • Place of Presentation: Taipei International Convention Center (Taipei, Taiwan)
  • Year and Date: 2016-10-06 – 2016-10-09
  • Int'l Joint Research / Invited
• [Presentation] Disseminated intravascular coagulation during eary phase of out-of-hospital cardiac arrest and resuscitation belongs to the fibrinolytic phonotype. (2016)
  • Author(s): Sadamoto Y, Katabami K, Wada T, Ono Y, Maekawa K, Hayakawa M, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01 – 2016-10-05
  • Int'l Joint Research
• [Presentation] Impact of age on the relationship between resuscitation duration and neurologically intact survival after out-of-hospital cardiac arrest. (2016)
  • Author(s): Maekawa K, Hayakawa M, Ono Y, Kodate A, Sadamoto Y, Tominaga N, Mizugaki A, Murakami H, Yshida T, Katabami K, Wada T, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01 – 2016-10-05
  • Int'l Joint Research
• [Presentation] The response time threshold for predicting favorable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest. (2016)
  • Author(s): Ono Y, Hayakawa M, Iijima H, Maekawa K, Kodate A, Sadamoto Y, Mizugaki A, Murakami H, Katabami K, Wada T, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01 – 2016-10-05
  • Int'l Joint Research
• [Presentation] Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with patients with out-of-hospital cardiac arrest. (2016)
  • Author(s): Kodate A, Katabami K, Wada T, Ono Y, Maekawa K, Hayakawa M, Sawamura A, Gando S.
  • Organizer: 29th Annual Congress of European Society of Intensive Care Medicine
  • Place of Presentation: MiCO Milano Congressi (Milano, Italy)
  • Year and Date: 2016-10-01 – 2016-10-05
  • Int'l Joint Research