| 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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