| Project/Area Number |
16K10676
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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 surgery
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| Research Institution | Mie University |
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Principal Investigator |
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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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 肺移植 / 心停止後臓器提供 / 薬剤性preconditioning現象 / heat shock protein / 臓器保存 / 虚血再灌流障害 / 細胞内シグナル伝達 / 外科 / 移植・再生医療 / シグナル伝達 |
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| Outline of Final Research Achievements |
Purpose: We hypothesized that exogenous heat shock proteins (HSPs) would provide pharmacological preconditioning (PPC). In the present study, we examined whether phosphorylated recombinant HSP27 (prHSP27), which recombinant HSP27 phosphorylated by MAPKAP kinase 2 in vitro, affected PPC to protect against lung ischemia-reperfusion (I/R) injury (LIRI). Methods: C57BL/6 mice received prHSP27(2.5 g/kg) or vehicle 30 minutes prior to 60 minutes of ischemia of their left lungs, followed by 180 minutes of reperfusion or ischemic preconditioning (IPC) with six cycles of 5 minutes ischemia and 5 minutes reperfusion prior to I/R. Results: Pretreatment of mice with prHSP27 resulted in the development of a significant smaller LIRI when compared with vehicle treated lungs. Conclusions: In this study, we demonstrated that prHSP27 migrates into lung tissue and maintains its activation. It suggests that prHSP27 may be a useful therapeutic agent to protect against LIRI as PPC.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦で臓器移植法が施行されてから22年が経過し、脳死肺移植も年々増加傾向にあるが、日本独自の社会通念や宗教観に基づく脳死下臓器提供は欧米と比して依然少ない。一方、脳死下臓器提供が一般的な欧米においても、移植医療の普及に伴い、昨今では慢性的なドナー不足が問題となっている。その打開策として心停止後臓器提供(DCD)が挙げられるが、虚血再灌流障害が障壁となり肺では稀である。DCDを可能すべく、長時間作動のpharmacological preconditioningの確立は今後の移植医療のみならず救急領域や周術期臓器保護においても大いに寄与すると考えられる。
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