2020 Fiscal Year Research-status Report
敗血症臓器障害におけるVEGFとアンジオポエチンの研究：短期型βブロッカーの作用
| Project/Area Number |
20K09282
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| Research Institution | University of Tsukuba |
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Principal Investigator |
河野 了 筑波大学, 医学医療系, 講師 (90323295)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | VEGF / アンジオポエチン / ランジオロール |
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| Outline of Annual Research Achievements |
In the first year of this project, we generated a rat sepsis model. Here, 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 VEGF system. In the current research, 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. Our previous study already confirmed that LPS-induced ALI showed significant morphological alteration in the lung with upregulation of both circulatory and pulmonary TNF-α and IL-6. LPS caused a significant 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. This treatment also considerably normalized the altered levels of blood gas parameters in sepsis rats. Here the downregulated VEGF has been recovered with landiolol treatment with its downstream signaling molecules. The present data suggest that landiolol treatment in LPS-administered rats plays an essential role in attenuating ALI through VEGF signaling normalization.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The current research is almost on the right track both from the contexts of timeline and the number of research activities scheduled to be done with the proper management of the project budget and research facilities available in the first year. We could successfully treat LPS-administered sepsis rats with landiolol. Last year we conducted studies on various duration of LPS-induced sepsis models and also did the dose-dependent study on landiolol. In our preliminary investigation, landiolol seems to be effective even at 3h treatment. So the current investigation was performed with 3h treatment of landiolol.
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| Strategy for Future Research Activity |
In the 2nd year of the project, we will concentrate on the angiopoietin system in various organs in sepsis animals. The effects of landiolol treatment will also be investigated. In addition, we will also examine the impact of landiolol on other tissues of sepsis models with the investigations of the VEGF system. In addition, we will use Tie-2 receptor knockout mice with sepsis induction and will study the effects of landiolol treatment.
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| Causes of Carryover |
新型コロナウイルス感染症拡大によって、予定していた試薬の一部が海外より入手できなかった。次年度は、予定通り入手し、研究を進める予定である。
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[Journal Article] Effects of Selective Endothelin Receptor Antagonist on Vegf Signaling System in Diabetic Penis: A Possible Clinical Implication for Diabetes Induced Erectile Dysfunction2021
Author(s)
Adil Maqbool, Subrina Jesmin, Chishimba N Mowa, Sayeeda Nusrat Sultana,Nobutake Shimojo, Yujiro Matsuishi, Takeru Shima, Naoto Yamaguchi, Takashi Miyauchi, Satoru Kawano, Takashi Miyauchi
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Journal Title
Cardiology & Vascular Research
Volume: 5
Pages: 1-7
Peer Reviewed / Open Access / Int'l Joint Research
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