| Project/Area Number |
18K06862
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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 48020:Physiology-related
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| Research Institution | Tsurumi University |
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Principal Investigator |
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 歯周病 / アポトーシス / 線維化 / 細胞内伝達 / ベータ受容体 / 心不全 / シグナル伝達 / リポポリサッカライド / ベータ遮断薬 / 心疾患 / ベータアドレナリン受容体 / サイクリックAMP / トランスジェニックマウス |
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| Outline of Final Research Achievements |
Lipopolysaccharide (LPS) is well known to activate Toll-like receptor 4 (TLR4) signaling and induce cardiac dysfunctions. The aim of the present study was to investigate the effects of LPS derived from Porphylomonas gingivalis (PG-LPS) on cardiac function in mice with or without an inhibitor of TLR4 signaling (TAK-242) for 4 weeks. Mice were divided into 4 groups:1) Control 2) PG-LPS-treated group, 3) TAK-242-treated group, and 4) PG LPS+TAK-treated groups. We first examined cardiac function by echocardiography and found that cardiac function was significantly decreased by the treatment of PG-LPS, but TAK-242 protected the dysfunction. Cardiac fibrosis (Masson-trichrome staining) and myocyte apoptosis (TUNEL staining) were significantly increased by the treatment of PG-LPS, but TAK-242 blocked these changes. These data suggest that chronic PG-LPS infusion might play an important role for the development of cardiac dysfunction via activation of TLR4 signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
歯周病と心疾患の関連性については、疫学的に関連があるという報告は多いが、一方で最近米国心臓病協会(AHA)より、因果関係について断定できる確証はないことが報告された (Lockhart PB et al. Circulation 2021)。本研究より歯周病の罹患を予防することは、健康寿命の延伸に重要であることが理解されれば、欧米諸国に比較して低い我国の歯科検診受診率は向上し(スウェーデン90%,アメリカ 80%,イギリス 70%, 日本6%)、日本歯科医師会と厚生労働省が推進する8020運動(80歳以上でも自分の歯を20本以上保つことで豊かな人生を)の達成率増加にも貢献すると期待される。
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