2022 Fiscal Year Final Research Report
Establishing the treatment of acute pancreatitis and pancreatic fistula utilizing the lipase inhibitor
Project/Area Number |
20K22948
|
Research Category |
Grant-in-Aid for Research Activity Start-up
|
Allocation Type | Multi-year Fund |
Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
|
Research Institution | Fujita Health University |
Principal Investigator |
|
Project Period (FY) |
2020-09-11 – 2023-03-31
|
Keywords | 膵液瘻 / リパーゼ / 脂肪 / 脂肪酸 |
Outline of Final Research Achievements |
We established a pancreatic fistula model using obese rats. Compared to the conventional animal model of pancreatic fistula by pancreatic transection in rats, the pathogenesis of pancreatic fistula was significantly exacerbated by adding thermal coagulation treatment to the adipose tissue, leading to decreased survival rates due to the effects of fat decomposition.
By mixing and adjusting the lipase inhibitor with polyethylene glycol in suitable ratios and conditions, it became possible to safely administer the lipase inhibitor intraperitoneally. Intraperitoneal administration of the lipase inhibitor alleviated the severity of pancreatic fistula in the aforementioned animal model. This provided a fundamental experimental basis for a novel therapeutic strategy involving the treatment of pancreatic fistula through the mechanism of fat decomposition inhibition.
|
Free Research Field |
消化器外科学
|
Academic Significance and Societal Importance of the Research Achievements |
腹部手術後の重大な合併症である膵液瘻はこれまで重症化メカニズムが不明で根本的な重症化予防法が存在しなかった。我々は脂肪分解という全く新しい膵液瘻重症化メカニズムを明らかにし、これに着目して脂肪分解酵素阻害剤を用いた膵液瘻重症化予防法の開発を行った。ラットを用いた重症化膵液瘻モデルを初めて確立した。また難水溶性分子である脂肪分解酵素阻害剤を生体適合性分子と適切に混合することで親水環境である腹腔内への投与が可能となった。開発した親水化脂肪分解酵素(リパーゼ)阻害剤を腹腔内投与することにより膵液瘻重症化防止が可能であることが動物モデルを用いた実験で示された。
|