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Development of infarction model induced by folic acid deficiency using a Microminipig atherosclerosis model

Research Project

Project/Area Number 16K08023
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Veterinary medical science
Research InstitutionKagoshima University

Principal Investigator

Kawaguchi Hiroaki  鹿児島大学, 医歯学域医学系, 准教授 (60325777)

Co-Investigator(Kenkyū-buntansha) 谷本 昭英  鹿児島大学, 医歯学域医学系, 教授 (10217151)
堀内 正久  鹿児島大学, 医歯学域医学系, 教授 (50264403)
Research Collaborator Fukushima Syouji  
Kanouchi Hiroaki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords動脈硬化 / マイクロミニピッグ / ミニブタ / 心筋梗塞 / 脳梗塞 / 葉酸 / 高ホモシステイン血症 / メトトレキサート / ホモシステイン / 梗塞病変 / ミニブタモデル / 病理学 / 循環器・高血圧 / 栄養学
Outline of Final Research Achievements

The aim of this study was development of myocardial and cerebral infarction models induced by folic acid deficiency using our atherosclerosis model induced by feeding a high fat and cholesterol diet (HFCD) for 8 weeks in Microminipigs. We investigated whether infarction was induced by the folic acid low-dosage high calorie diet feeding (FAL-HCD) and HFCD feeding with administration of methotrexate (MTX). HFCD+MTX induced hyperhomocysteinemia, hypofolate and acceleration of arteriosclerosis in aorta while FAL-HCD couldn’t induce hyperhomocysteinemia and hypofolate.
Further studies are required to develop myocardial and cerebral infarction models of minipig, and to reveal the mechanism of arteriosclerosis acceleration induced by MTX.

Academic Significance and Societal Importance of the Research Achievements

日本の死因の上位を占める心筋梗塞および脳梗塞の主因は動脈硬化である。我々のヒトの生活習慣に準じた食餌制御性マイクロミニピッグ動脈硬化症モデルに、さらにヒトの生活習慣に起因する負荷を加え、梗塞を促進するモデルを開発することは、病態の機序解明や疾病の克服に貢献し、社会的意義は大きい。
本研究では心筋梗塞・脳梗塞モデルの開発には至らなかったが、開発のための改善点もみえてきた。また、メトトレキサート投与を負荷することにより、動脈硬化が増悪されたことが新たに発見され、今後この機序を解明することも、梗塞モデルへの発展にもつながり、学術的意義は大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs2017

    • Author(s)
      Yamada S, Kawaguchi H, Yamada T, Guo X, Matsuo K, Hamada T, Miura N, Tasaki T, Tanimoto A.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 24 Issue: 11 Pages: 1150-1166

    • DOI

      10.5551/jat.39909

    • NAID

      130006191597

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery.2017

    • Author(s)
      Zahorul Islam M, Kawaguchi H, Miura N, Miyoshi N, Yamazaki-Himeno E, Shiraishi M, Miyamoto A, Tanimoto A.
    • Journal Title

      Microvasc Res

      Volume: 114 Pages: 52-57

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Corpus luteum Regression Induced by Prostaglandin F2α in Microminipigs During the Normal Estrous Cycle.2017

    • Author(s)
      Noguchi M, Hirata M, Kawaguchi H, Tanimoto A.
    • Journal Title

      In Vivo

      Volume: 31 Pages: 1097-1101

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential predictors of susceptibility to occupational stress in Japanese novice nurses - a pilot study.2017

    • Author(s)
      Okita S, Daitoku S, Abe M, Arimura E, Setoyama H, Koriyama C, Ushikai M, Kawaguchi H, Horiuchi M.
    • Journal Title

      Environ Health Prev Med

      Volume: 22 Issue: 1 Pages: 20-20

    • DOI

      10.1186/s12199-017-0641-8

    • NAID

      210000130209

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System.2017

    • Author(s)
      Sato M, Miyoshi K, Nakamura S, Ohtsuka M, Sakurai T, Watanabe S, Kawaguchi H, Tanimoto A.
    • Journal Title

      Int J Mol Sci

      Volume: 18 Issue: 12 Pages: 2610-2610

    • DOI

      10.3390/ijms18122610

    • NAID

      120007099791

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Birth of Cloned Microminipigs Derived from Somatic Cell Nuclear Transfer Embryos that have been Transiently Treated with Valproic Acid.2016

    • Author(s)
      Miyoshi K, Kawaguchi H, Maeda K, Sato M, Akioka K, Noguchi M, Horiuchi M, Tanimoto A.
    • Journal Title

      Cellular Reprogramming

      Volume: 18 Pages: 390-400

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Estrus synchronization in microminipig using estradiol dipropionate and prostaglandin F<sub>2α</sub>2016

    • Author(s)
      Nogcuhi M., Ikedo T., Kawaguchi H., Tanimoto A
    • Journal Title

      Journal of Reproduction and Development

      Volume: 62 Issue: 4 Pages: 373-378

    • DOI

      10.1262/jrd.2015-169

    • NAID

      130005406792

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs.2016

    • Author(s)
      Morishita S, Kawaguchi H, Ono T, Miura N, Murakoshi M, Sugiyama K, Kato H, Tanimoto A, Nishino H.
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 80 Pages: 295-303

    • Related Report
      2016 Research-status Report
    • Open Access
  • [Journal Article] Microminipigs as a new experimental animal model for toxicological studies: comparative pharmacokinetics of perfluoroalkyl acids.2016

    • Author(s)
      Guruge KS, Noguchi M, Yoshioka K, Yamazaki E, Taniyasu S, Yoshioka M, Yamanaka N, Ikezawa M, Tanimura N, Sato M, Yamashita N, Kawaguchi H.
    • Journal Title

      J Appl Toxicol

      Volume: 36 Issue: 1 Pages: 68-75

    • DOI

      10.1002/jat.3145

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 犬の輸送ストレス軽減のための新規鍼治療の試み.2016

    • Author(s)
      川口博明, 笹竹 洋, 野口倫子, 秋岡幸兵, 三浦直樹, 武石嘉一朗, 堀内正久, 谷本昭英.
    • Journal Title

      日本獣医師会雑誌

      Volume: 69 Pages: 143146-143146

    • NAID

      130005147266

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] NOS阻害剤投与による超短期マイクロミニピッグ動脈硬化モデルの開発2019

    • Author(s)
      川口博明, 谷本昭英
    • Organizer
      第35回 日本毒性病理学会総会および学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 行性動物マイクロミニピッグにおける無麻酔下経時的脳脊髄液採取法の確立.2018

    • Author(s)
      川口博明, 阿部正治, 牛飼美晴, 大井紗弓, 柚川藍色, 吉川哲也, 和泉博之, 谷本昭英, 堀内正久.
    • Organizer
      第34回日本毒性病理学会総会及び学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ミニブタを用いた食事によるヒト生活習慣病モデルの研究.2018

    • Author(s)
      川口博明, 叶内宏明, 佐藤元彦.
    • Organizer
      第6回あしなが予防医学研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] レプチン受容体欠損マウスを用いた時期特異的レプチンシグナル動態の解析.2017

    • Author(s)
      牛飼美晴, Pulong Wijang Pralampita, 阿部正治, 川口博明, 有村恵美, 中熊美和, 堀内正久.
    • Organizer
      第87回日本衛生学会学術総会
    • Place of Presentation
      宮崎県シーガイヤ・コンベンションセンター(宮崎県宮崎市)
    • Year and Date
      2017-03-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 高たんぱく低炭水化物食と低たんぱく高炭水化物食が腎機能・窒素代謝に及ぼす影響.2017

    • Author(s)
      有村恵美, 中熊美和,  阿部正治, 牛飼美晴, 川口博明, 堀内正久.
    • Organizer
      第20回日本病態栄養学会年次学術集会
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2017-01-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 削蹄のいらないミニブタ用床材の開発.2017

    • Author(s)
      川口博明, 秋岡幸兵, 阿部正治, 牛飼美晴, 松尾 恵, 堀内正久, 谷本昭英.
    • Organizer
      第35回九州実験動物研究会総会/第37回日本実験動物技術者協会研究発表会.
    • Related Report
      2017 Research-status Report
  • [Presentation] ミニブタを用いた食事・光による生体リズムへの影響解析.2017

    • Author(s)
      川口博明, 武石嘉一朗, 阿部正治, 有村恵美, 牛飼美晴, 堀内正久.
    • Organizer
      第87回日本衛生学会学術総会
    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Presentation] ICTによる24時間牛体温遠隔モニターシステムの開発.2017

    • Author(s)
      川口博明, 安藤貴朗, 畑添至, 入來俊久, 古賀周治, 山田峰也, 中武貞文, 小澤真, 三浦直樹, 谷本昭英.
    • Organizer
      第160回日本獣医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 食事蛋白質量が2型糖尿病網膜症に及ぼす影響~レプチン受容体欠損マウスを用いた検討~2016

    • Author(s)
      有村恵美, 岡谷秀明, 荒木智陽, 川口博明, 中熊美和, 阿部正治, 牛飼美晴, 和泉博之, 堀内正久.
    • Organizer
      第54回日本糖尿病学会九州地方会
    • Place of Presentation
      かごしま県民交流センター(鹿児島県鹿児島市)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Research-status Report
  • [Presentation] マイクロミニピッグの毒性病理2016

    • Author(s)
      川口博明, 堀内正久, 谷本昭英
    • Organizer
      第43回日本毒性学会学術集会
    • Place of Presentation
      ウインクあいち(愛知県産業労働センター)(愛知県名古屋市)
    • Year and Date
      2016-06-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] マイクロミニピッグにおける高塩分食摂取の生体応答.2016

    • Author(s)
      武石嘉一朗, 川口博明, 笹竹洋, 阿部正治, 牛飼美晴, 有村恵美, 谷本昭英, 堀内正久.
    • Organizer
      第86回日本衛生学会学術総会
    • Place of Presentation
      旭川市民文化会館(北海道旭川市)
    • Year and Date
      2016-05-11
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 動物用床材2018

    • Inventor(s)
      川口博明
    • Industrial Property Rights Holder
      川口博明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 動物用床材2017

    • Inventor(s)
      川口博明、谷本昭英
    • Industrial Property Rights Holder
      川口博明、谷本昭英
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 動物用床材2017

    • Inventor(s)
      川口博明
    • Industrial Property Rights Holder
      川口博明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-02-15
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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