The elucidation of the exacerbating factors for pancreatic fistula and therapeutic application based on the prevention of intraperitoneal lipolysis
| Project/Area Number |
18K08702
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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 55020:Digestive surgery-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
増井 俊彦 京都大学, 医学研究科, 客員研究員 (20452352)
上本 伸二 滋賀医科大学, 医学部, 学長 (40252449)
田畑 泰彦 京都大学, ウイルス・再生医科学研究所, 教授 (50211371)
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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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膵手術 / 膵液瘻 / 遊離脂肪酸 / 不飽和脂肪酸 / 膵液瘻重症化因子 / リパーゼ阻害 / PEG / 脂肪分解 / 膵切離 / 膵切除 / 術後合併症 / ゲル / ラットモデル / 重症化 / 脂肪酸 |
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| Outline of Final Research Achievements |
In pancreatic fistula, intraabdominal fat has been reported to be the aggravating factor of the clinical condition. We have confirmed that serum free fatty acids (FFAs) produced by lipolysis of triglycerides caused systemic inflammatory response, and aggravated the condition of pancreatic fistula in a rat model of pancreatic transection; lipase inhibitors reduced the toxicity of FFAs. We next developed a rat model of clinically relevant pancreatic fistula (CRPF) using intraabdominal administration of autologous fat-dissolver, and evaluated the efficacy of hydrogel mixture of emulsion containing lipase inhibitor encapsulated by polyethylene glycol (PEG) as a drug with high practicability. Intraperitoneal production of FFAs worsened survival in CRPF rats, and the application of the hydrogel mixture of lipase inhibitor with PEG dose-dependently improved survival by reducing the production of intraabdominal FFAs. These results indicate a new therapeutic strategy for pancreatic fistula.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ラット膵切離・膵液瘻モデルを用いて、膵酵素の脂肪分解による遊離脂肪酸産生が膵液瘻における病態増悪因子として寄与すること、またリパーゼ阻害薬による脂肪分解抑制が膵液瘻増悪を防ぐという結果を得た。本研究の成果から膵液瘻に対する新規治療法開発につながる可能性が期待される。
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Report
(6 results)
Research Products
(10 results)
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[Journal Article] Impact of vascular abnormality on contrast-enhanced CT and high C-reactive protein levels on postoperative pancreatic hemorrhage after pancreaticoduodenectomy: A multi-institutional, retrospective analysis of 590 consecutive cases2021
Author(s)
Yuichiro Uchida, Toshihiko Masui, Kazuki Hashida, Takafumi Machimoto, Kenzo Nakano, Akitada Yogo, Asahi Sato, Kazuyuki Nagai, Takayuki Anazawa, Kyoichi Takaori, Shinji Uemoto
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Journal Title
Pancreatology
Volume: 21
Issue: 1
Pages: 263-268
DOI
Related Report
Peer Reviewed
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