| Project/Area Number |
16K10089
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Kindai University (2019)
Osaka University (2016-2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田附 裕子 大阪大学, 医学系研究科, 准教授 (10397698)
奥山 宏臣 大阪大学, 医学系研究科, 教授 (30252670)
児玉 匡 大阪大学, 医学部附属病院, 医員 (60771045)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 壊死性腸炎 / 新生児 / 補体 / 治療 / 低出生体重児 / 可溶性トロンボモジュリン / 保体 / NEC |
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| Outline of Final Research Achievements |
NEC remains the leading cause of death in preterm infants. The aim of this study was to evaluate the effect of Recombinant human soluble thrombomodulin (rTM) in a NEC model. NEC was induced by enteral feeding with hyperosmolar formula, gavage administration of lipopolysaccharide and asphyxia stress. In the treatment group, rTM was administered subcutaneously twice . The ileum was harvested for a histological evaluation and the measurement of the mRNA and protein expression. The rate of NEC-like intestinal injury in the treatment group (36%) was significantly lower than in the NEC group (73.5%). Tissue levels of TNF-alpha, IL-6 and HMGB1 were significantly elevated in the NEC group, whereas those in the treatment group were decreased to similar values as in the control group. Our experimental study showed that rTM is able to reduce the severity and incidence of NEC. It may be an alternative option for the treatment of NEC.
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| Academic Significance and Societal Importance of the Research Achievements |
壊死性腸炎（NEC）は，低出生体重児・早産児の死亡原因となる重篤な疾患である．周産期管理の向上により生存率は改善しているがさらなる生存率および予後の改善が望まれている．新しい治療法の開発のため実験的研究を行った．抗炎症効果および抗凝固効果のある可溶性トロンボモジュリン（rTM）に着目し実験的NECモデルにおいて治療効果を検討した．長官の組織傷害は治療群において改善し，腸管における炎症性サイトカインのTNF-α，IL-6のmRNA発現は低下した．rTMによる治療はNECの発症や重症度を軽減し治療選択肢の一つとなりうる可能性が示された．
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