| 研究課題/領域番号 |
20K09282
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| 研究機関 | 茨城県立医療大学 |
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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 – 2023-03-31
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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 |
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| 研究実績の概要 |
We also extended the research on sepsis-induced ALI (acute lung injury) in the 2nd year. In the 2nd year, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, has any vital role in lessening LPS-induced ALI (acute lung injury) by altering the angiopoietin-2. Indeed, angiopoietin-2 is an endothelium-specific growth factor and is regulated by proinflammatory stimuli with a destabilization of vascular endothelium and an increase in vascular leakage. We used male Wistar rats at 8weeks 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. This experimental setting has already validated LPS-induced ALI with significant morphological alteration in the lung, upregulated both circulatory and pulmonary TNF-α and IL-6, and upregulation of pulmonary level of angiopoietin-2. These changes accompanied an LPS-induced considerable decrease in pulmonary levels of VEGF with Pa02. Here we found that the treatment of LPS-administered rats with landiolol for 3h significantly stopped the progression of ALI with marked normalization of angiopoietin-2. This treatment also considerably normalized blood gas parameters, and pulmonary downregulated VEGF levels. Collectively, our data indicate that landiolol treatment in LPS-administered rats plays an essential role in attenuating ALI 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 first two 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. We could have all reagents available to conduct the studies. We could reproduce data in first and second years of the experiment. All experiments were based on time-course and dose-dependent studies. Thus the time point and the dose were validated in both of these years for the experimental setting.
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| 今後の研究の推進方策 |
In the 3rd year of the project, we will continue the investigation of VEGF and angiopoietin system in various organs in sepsis animals besides lung tissues. Heart, kidney, liver, and brain are essential to be investigated. The effects of landiolol treatment will also be simultaneously explored. We will also aim to use Tie-2 receptor knockout mice in the current experimental setting with sepsis induction and examine the effects of landiolol treatment.
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| 次年度使用額が生じた理由 |
新型コロナウイルス感染症の蔓延のため、予定していた学会に参加できず、旅費が使用できなかった。次年度は、様子を見て参加できるなら旅費を使用する予定である。
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