| Project/Area Number |
16K10111
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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 | Kitasato University (2017-2019)
Tokyo Women's Medical University (2016) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北原 秀治 東京女子医科大学, 医学部, 講師 (40510235)
森川 俊一 東京女子医科大学, 医学部, 講師 (70339000)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 慢性肺疾患 / 早産児 / 肺胞微小血管 / 血液空気関門 / 血管内皮細胞 / 微小血管障害 / 血管再生 / Angiopoietin-1 / 未熟児医学 |
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| Outline of Final Research Achievements |
Considering that administration of Angiopoietin-1 (Ang-1), which plays an important role in angiogenesis, will lead to a new therapeutic strategy for bronchopulmonary dysplasia in premature infants, we studied ultrastructural changes in pulmonary microvasculature after Ang-1 administration, by using lungs from newborn mice exposed to hyperoxia for 14days after birth followed by 7 days of normal room-air replacement conditions.
As a result, Ang-1 administration dramatically improved vascular endothelial cell morphology abnormalities and blood-air barrier thickening. Along with this, the alveolar structural abnormality was also improved and the right ventricular myocardial weight, an index of secondary pulmonary hypertension, was reduced. The involvement of immune-related genes was suggested as the background of the effect of improving microvascular injuries.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で我々は、発達期肺障害における主要な障害部位は、肺胞壁内の微小血管であり血液空気関門を構成する血管内皮細胞であることを解明した。またAngiopoietin-1（Ang-1）投与により、血管内皮細胞障害の改善とともに肺胞構造異常と二次性肺高血圧の改善を認めたことから、Ang-1がCLDの新たな治療戦略となる可能性が示唆された。また効果の背景に免疫関連遺伝子の関与が示唆されたことより、血管再生と免疫修飾の両面からのシグナル修飾が新たなCLD治療戦略となる可能性も示唆された。
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