| Project/Area Number |
17K10508
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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 |
General surgery
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| Research Institution | University of Yamanashi |
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Principal Investigator |
KONO Hiroshi 山梨大学, 大学院総合研究部, 准教授 (40322127)
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| Co-Investigator(Kenkyū-buntansha) |
雨宮 秀武 山梨大学, 大学院総合研究部, 助教 (70377547)
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| Project Period (FY) |
2017-04-01 – 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 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 細菌性腹膜炎 / 下垂体ポリペプチド / 肺障害 / マクロファージ / サイトカイン / 細菌性腹膜 / 細菌性髄膜炎 |
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| Outline of Final Research Achievements |
The purpose of this study was to investigate effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in sepsis. Mice were given PACAP before or after cecal ligation and puncture (CLP), and organ injury and mortality were investigated. Serum inflammatory and anti-inflammatory cytokine levels were assessed. Isolated tissue macrophages (Mfs) were incubated with or without PACAP, and production of cytokines was measured. PACAP treatment significantly prevented mortality after CLP. Increased serum TNF-a and HMGB1 levels in animals treated with vehicle were significantly blunted in PACAP-treated animals after CLP. Serum IL-10 levels were significantly greater in the PACAP-treated group compared with the vehicle group. Production of HMGB1 and TNF-a by isolated hepatic Mfs was significantly inhibited in the presence of PACAP, while production of IL-10 by isolated KCs and interstitial lung Mfs was significantly increased. PACAP prevents mortality due to septic peritonitis.
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| Academic Significance and Societal Importance of the Research Achievements |
腹部救急の領域において大腸穿孔に代表される細菌性腹膜炎は治療に難渋することが多く、多臓器不全を発症し、致死率の非常に高い病態である。局所の炎症の制御は、手術的なドレナージが最も有効であるが、予後に強く寄与する肺や肝臓などの遠隔臓器での多臓器障害を制御する目的での薬物投与による有効な治療方法は未だ確立されていない。PACAP投与の抗炎症作用の有効性に関する視点から検討はこれまで無く、今回の検討成果は細菌性腹膜炎に伴う、多臓器障害改善に対する新しい治療の開発に発展する可能性を持つ。今後、炎症・感染おける生体侵襲を科学的に解明し、その制御を目指すという視点からの研究につながると考える。
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