| Project/Area Number |
18K08258
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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 53040:Nephrology-related
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| Research Institution | Aichi Medical University |
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Principal Investigator |
Ito Yasuhiko 愛知医科大学, 医学部, 教授 (60402632)
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| Co-Investigator(Kenkyū-buntansha) |
水野 正司 名古屋大学, 医学系研究科, 特任教授 (20303638)
勝野 敬之 愛知医科大学, 医学部, 准教授 (60642337)
武井 佳史 愛知学院大学, 薬学部, 教授 (70362233)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腎不全 / 腹膜透析 / 腹膜機能 / glycocalyx / 塩 / 腹膜透過性 / 内皮細胞 / Glycocalyx / 食塩 / TonEBP / IL-6 / 透過性亢進 / D/P Cr / 炎症 / TGF-b-VEGF-C pathway / 除水不全 / 腹膜機能障害 |
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| Outline of Final Research Achievements |
Peritoneal dialysis is a blood purification method that uses a biological membrane called peritoneum as a dialysis membrane. Peritoneal permeability is known to be an important factor in determining prognosis. Although the mechanism has been attributed to an increase in the number of blood vessels, contradictory findings have become apparent. In this study we found that abnormalities in the glycocalyx of peritoneal capillaries and a decrease in heparan sulfate and UEA-I lectin-binding sugar chains are associated with increased permeability. In addition, we found that excessive salt intake causes sodium accumulation in soft tissues and activates TonEBP, which in turn induces MCP-1 expression, macrophage infiltration, IL-6 upregulation, inflammation and angiogenesis, leading to increase of vascular permeability. It is expected to become a therapeutic target in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
腹膜透析は、腹膜という生体膜を透析膜として用いる血液浄化法で近年循環動態への影響が少ないことから高齢者に適しているといわれている。腹膜透過性亢進が予後を決定する重要因子であることが明らかとされているが、その機序は不明なところが多い。今回、腹膜の毛細血管のglycocalyx異常、食塩摂取過剰から炎症が惹起され血管新生・透過性亢進の機序を明らかとした。治療ターゲットとなり、治療の質向上および除水不全の改善から離脱がへることが期待される。このことは、腹膜透析患者にとって朗報となりまた医療費削減にもつながると考える。
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