| Project/Area Number |
16K09532
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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 |
Respiratory organ internal medicine
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安尾 将法 信州大学, 学術研究院医学系(医学部附属病院), 講師 (20402117)
北口 良晃 信州大学, 医学部附属病院, 助教(診療) (40447751)
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| Research Collaborator |
WADA Yosuke
YUNDEN Droma
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 第3群肺高血圧症 / 肺気腫 / VEGF受容体阻害薬 / 低酸素 / ラット / 3群肺高血圧症 / 血管内皮成長因子受容体阻害薬 / タバコ抽出液 |
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| Outline of Final Research Achievements |
The rats treated with vascular endothelial growth factor (VEGF) receptor blocker, SU5416, developed emphysema. Moreover, the SU5416/hypoxia/normoxia-exposed rats developed severe pulmonary hypertension (PH) of group 1 with progressive proliferation of pulmonary arterial endothelial cells. The aim of this study attempts to establish a rat model of PH in association with emphysema. Male Sprague-Dawley rats were injected subcutaneously with SU5416 on day 1, 8 and 15, and exposed to normobaric hypoxia for 6 weeks. The results showed that the airspaces (mean linear intercept) were significantly enlarged, suggesting development of emphysema. Furthermore, the SU5416/hypoxia rats showed significantly increased mean pulmonary arterial pressure. The present study suggested that the exposure of the rats treated with VEGF receptor inhibitor to hypoxia induced PH that was highly associated with emphysema. This novel animal model is mimic of the pathophysiological changes of group 3 PH in humans.
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| Academic Significance and Societal Importance of the Research Achievements |
肺疾患に伴う肺高血圧症（第3群肺高血圧症）は患者数が多く、予後不良であるが、酸素療法以外に有効性が証明された治療はない。第3群肺高血圧症の動物モデルは現在まで報告がなく、肺気腫合併肺高血圧症モデルが完成すれば、病態の解明や治療戦略の構築に寄与する。本研究により、既に第1群肺高血圧症（肺動脈性肺高血圧症）に使用されている選択的肺血管拡張薬の有効性が証明され、さらに肺血管選択性の高い薬剤送達システムについて新たな知見が得ることができれば、難治性の第3群肺高血圧症の診療に道が開け、臨床応用への期待が高まる。
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