| Project/Area Number |
18K08101
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Mie University |
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Principal Investigator |
DOHI KAORU 三重大学, 医学系研究科, 教授 (50422837)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 正明 三重大学, 医学系研究科, 教授 (00223181)
岡本 隆二 三重大学, 医学部附属病院, 教授 (60378346)
片山 鑑 三重大学, 医学部附属病院, 講師 (90742247)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 循環器 / 食塩感受性 / SGLT2阻害薬 |
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| Outline of Final Research Achievements |
Dahl salt-sensitive (DSS) hypertensive rats were treated orally for 8-weeks with normal salt diet (0.3% NaCl), high salt diet (8% NaCl), high salt diet with SGLT2 inhibitor (ipragliflozin 0.04%), high salt diet with ARB (losartan 0.05%), or high salt diet with combination treatment. Only the combination treatment lower blood pressure and improved salt-sensitivity. The combination treatment significantly ameliorated glomerulosclerosis, and reduced cardiomyocyte hypertrophy and perivascular fibrosis. Angiotensin II type 1 receptor (AT1R) protein expression level in the kidney was remarkably suppressed in the combination treatment group compared to the other high salt diet groups. The protein expression level of Na+/H+ exchanger isoform 3 and Na+-K+-Cl- cotransporter 2 were significantly decreased with losartan alone and combination with ipragliflozin.
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| Academic Significance and Societal Importance of the Research Achievements |
近年の大規模臨床研究では糖尿病患者のみならず非糖尿病患者におけるSGLT2阻害薬の心不全抑制効果・腎保護効果が証明されているが、これらの研究ではRAA系阻害薬併用率は80%を超えており、併用療法の心・腎組織への作用機序解明が急がれる。本研究ではDahl食塩感受性高血圧ラットを用いてSGLT2阻害薬とARBの併用が食塩感受性亢進状態に抑制的に作用することを証明するとともに、心・腎障害抑制の分子機序の一端解明した。
本研究の成果は今後の心不全診療、腎不全診療の発展に寄与するものと思われる。
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