2022 Fiscal Year Final Research Report

The elucidation of the exacerbating factors for pancreatic fistula and therapeutic application based on the prevention of intraperitoneal lipolysis

Research Project

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Project/Area Number	18K08702
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Kyoto University
Principal Investigator	Nagai Kazuyuki 京都大学, 医学研究科, 講師 (30567871)
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)
Project Period (FY)	2018-04-01 – 2023-03-31
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
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.
Free Research Field	膵臓外科
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。