2018 Fiscal Year Final Research Report

The role of angiopoietin-2 in anaphylactic shock

Research Project

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Project/Area Number	16K11428
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Emergency medicine
Research Institution	Kanazawa Medical University
Principal Investigator	SHIBAMOTO Toshishige 金沢医科大学, 医学部, 教授 (90178921)
Co-Investigator(Kenkyū-buntansha)	九田裕一金沢医科大学, 医学部, 助教 (50566916) 谷田守金沢医科大学, 医学部, 准教授 (70512309)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	Angiopoietin 2 / アナフィラキシーショック / マウス / ラット / 血管透過性亢進 / ヘマトクリット
Outline of Final Research Achievements	Angiopoietin (Angpt)-2, an endothelium derived permeability-increasing factor, is involved in vascular leakage of sepsis, but its role remains unknown in anaphylactic hyperpermeability. We determined plasma Angpt-2 levels and hematocrit (Hct) as a measure of vascular leak during anaphylactic hypotension in ovalbumin-sensitized mice and rats. In both animals, following antigen injection, vascular permeability increased at 20 min, and Hct increased reaching the peak within 20 min, followed by a progressive decrease in rats. The plasma Angpt-2 levels did not change significantly within 20 min and until 60 min in mice and rats, respectively. Thereafter, in awake rats, they reached the peak at 6 h after antigen, and returned to the baseline at 24 h. In addition, in mice, western blot analysis revealed no increase in tissue Angpt-2 within 20 min after antigen. In conclusion, Angpt-2 is not released at early phase when vascular leak occurs during anaphylactic hypotension in mice and rats.
Free Research Field	生理学
Academic Significance and Societal Importance of the Research Achievements	アナフィラキシーショックは致死的となりうる救急疾患で、更なる病態解明が求められている。その病態の特徴として血管透過性亢進がある。本研究の目的は敗血症などの血管透過性亢進に関わるAngiopoietin(Angpt)-2がアナフィラキシーへの関与を動物実験で解明することであった。その結果、ラットとマウスともにアナフィラキシー低血圧時に血管透過性は抗原投与20分以内の早期に亢進したが、その時にはAngpt-2の血中と組織中の濃度増加はなく、血管透過性亢進への関与は低いことが明らかとなった。本研究成果は致死的病態であるアナフィラキシー低血圧時の血管透過性亢進の病態の解明に貢献するものと考えられる。