研究課題/領域番号 |
20K09282
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研究種目 |
基盤研究(C)
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配分区分 | 基金 |
応募区分 | 一般 |
審査区分 |
小区分55060:救急医学関連
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研究機関 | 茨城県立医療大学 (2021-2022) 筑波大学 (2020) |
研究代表者 |
河野 了 茨城県立医療大学, 付属病院, 教授 (90323295)
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研究分担者 |
下條 信威 筑波大学, 医学医療系, 講師 (20462210)
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研究期間 (年度) |
2020-04-01 – 2024-03-31
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研究課題ステータス |
交付 (2022年度)
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配分額 *注記 |
4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円)
2022年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2021年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2020年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
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キーワード | VEGF / アンジオポエチン / ランジオロール |
研究開始時の研究の概要 |
本プロジェクトはVEGFとアンジオポエチンの関連性、またランジオロールの効果を明らかにするため、in vivoの基礎研究から人間を対象とした臨床研究に至るまで広い範囲で研究を行う。 研究1:ラットはWistar ST、8~12週齢、250-300gを敗血症モデルに使用する。LPSは15mg/Kgを頸静脈より静脈注射する。 研究2:Tie2受容体ノックアウトマウスを使用し、LPSを投与し敗血症モデルとする。 臨床研究(研究3):対象病院に入院した早期敗血症患者でありランジオロールを投与している患者を対象とし、血中VEGFとアンジオポエチンを評価する。
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研究実績の概要 |
We completed 3 years of this research. With working on acute lung injury, we also did many experiments on LPS-induced myocardial dysfunction and liver injury. Morphologically, landiolol hydrochloride, an ultra-short-acting β-blocker, plays vital role in lessening LPS-induced cardiac and liver injury. We used male Wistar rats at 8 weeks of age and were administered with either saline or lipopolysaccharide (LPS) for three hours (3h), and some of the LPS-administered rats were continuously treated with landiolol for 3h, extending experiments for 6h and 10h. We have seen the changes in both circulatory and tissue TNF-α and IL-6 with alteration of level of angiopoietin-2 in heart and liver. These changes were accompanied an LPS-induced considerable alteration in cardiac and liver levels of VEGF with Pa02. Here we found that the treatment of LPS-administered rats with landiolol starting from 3h significantly stopped the progression of cardiac dysfunction and liver injury with marked normalization of angiopoietin-2. This treatment also considerably normalized blood gas parameters, and tissue VEGF levels. Collectively, our data indicate that landiolol treatment in LPS-administered rats plays an essential role in attenuating cardiac dysfunction and liver injury through modulation of angiopoietin-2 with concomitant VEGF signaling reversal.
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現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We are on the planned activities of the research with the target milestone. The current study is almost on the right track, both from the context of the timeline and the number of research activities scheduled to be done to properly manage the project budget and research facilities available for the three years. We did not face any technical difficulties. Although Covid has impacted many things, we were careful to perform every target of the project with excellent efficiency and impact. The model generation was successful. We could successfully treat LPS-administered sepsis rats with landiolol. We could have all reagents available to conduct the studies. Of note, all these experiments were based on time-course and dose-dependent studies. Thus the time point and the dose were validated in these years for the experimental setting.
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今後の研究の推進方策 |
We are still continuing this work on in vitro cell culture and knockout mice. Also, we are working on kidney and brain.
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