2022 Fiscal Year Final Research Report
Elucidation of the pathophysiology of brain death-related lung injury and development of precaution and remedy -especially in relation to NPY and VEGF
| Project/Area Number |
19K09325
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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 55050:Anesthesiology-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 神経原性肺水腫 / 神経ペプチドY / 気管支上皮細胞 / 細胞透過性 / ラット脳死モデル / 脳死肺移植 |
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| Outline of Final Research Achievements |
The aim of the present study was to clarify the action mechanism of neuropeptide Y (NPY), which was considered to be related to the cell permeability in neurogenic pulmonary edema (NPE) in brain death patients, using in vitro cell permeability evaluation system of human bronchial epithelial Calu-3cell line and in vivo brain death-induced pulmonary edema rat model.
Due to difficulties in obtaining cell culture inserts made overseas, we tried to reconstruct a lung epithelial cell permeability evaluation system using Calu-3. Although we evaluated the effects of cytotoxic LPS on cell permeability increase both in Calu-3 cell monolayer alone and when co-cultured with macrophage-like cells, we could not find the appropriate culture conditions and decided to abandon the construction of the assay system using Calu-3 cells. On the other hand, in establishing in vivo model, we found the optimal rat treatment method that produced pulmonary edema after brain death induction.
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| Free Research Field |
医歯薬学、外科系臨床医学、麻酔学
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| Academic Significance and Societal Importance of the Research Achievements |
臓器移植医療において、たとえ脳死患者側が肺を提供臓器として了解していたとしても肺障害のため移植手術に至らない場合が多い。その原因として、肺炎以外に脳浮腫・脳圧亢進による神経原生肺水腫の関与が報告されている。すでに研究代表者は、ラット肺水腫モデルにおいて神経ペプチドY （NPY）の肺血管透過性亢進作用を見出している。本研究では、NPYの作用機序を解明するための評価系作製を試みたが、系を確立するには及ばなかった。しかしながら、in vivo脳死誘発肺水腫モデルラット作製方法習得など、研究自体は大きく前進した。今後の肺障害発生機序の解明研究により、脳死患者の肺障害予防法・治療法の開発が期待される。
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