| Project/Area Number |
18K08785
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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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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TOBA Hiroaki 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (40403745)
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| Co-Investigator(Kenkyū-buntansha) |
川上 行奎 徳島大学, 病院, 特任講師 (00596249)
河北 直也 徳島大学, 病院, 講師 (60522266)
森本 雅美 徳島大学, 病院, 特任助教 (90563817)
谷原 史倫 自治医科大学, 医学部, 准教授 (90754680)
平田 真樹 徳島大学, バイオイノベーション研究所, 講師 (10815583)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 急性肺障害 / 肺の修復・再生 / p53遺伝子改変ブタ / 肺オルガノイド |
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| Outline of Final Research Achievements |
We used lipopolysaccharide(LPS)-induced acute lung injury porcine model for this study. Under general anesthesia, LPS was selectively administrated intratracheally into the right anterior lobe by using bronchoscope in both wild type and p53 KO groups. Computed tomography (CT) already showed the infiltrations at 6 hours (hrs) and consolidations at 48 hrs after administration in the lung fields of both groups. At 6 hrs after LPS administration, the pulse rate was significantly decreased in p53 KO group. In both groups, the findings of acute lung injury were histologically confirmed. Some cytokines and chemokines were measured by using samples of serum and bronchoalveolar lavage (BAL), and TNF-alfa, IL-6 and IL-10 were increased at 6 hrs after LPS administration in p53 KO group. Additionally, we tried to form the organoids from porcine lung. We could collect basal cell marker positive cells, and confirm the formation of the organoids-like structures under 3-doimention culture for 14 days.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究においては，解剖学的・生理学的にヒトに近いブタ，特にp53 KOブタを用いて，p53が急性気道・肺胞上皮の障害・再生にどのような役割を果たすかどうかについて明らかにすることであった．LPS誘導急性肺障害モデルを用いた結果から，p53が肺障害による悪影響から守る役割を果たしている可能性が示唆された．このことから，大動物における肺障害においてのp53の役割に関する知見の一端を初めて明らかにすることができたと考える．
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