ID | 64141 |
フルテキストURL | |
著者 |
Nojima, Tsuyoshi
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
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Obara, Takafumi
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamamoto, Hirotsugu
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yumoto, Tetsuya
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
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Igawa, Takuro
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Aokage, Toshiyuki
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Seya, Mizuki
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakao, Atsunori
Department of Emergency, Critical Care, and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | Background: Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemiareperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury.
Methods: Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 mM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation. Results: Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P 1/4 .030). Conclusion: This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation. |
発行日 | 2022-11
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出版物タイトル |
Surgery
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巻 | 172巻
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号 | 5号
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出版者 | Elsevier BV
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開始ページ | 1522
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終了ページ | 1528
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ISSN | 0039-6060
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NCID | AA00853880
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2022 The Author(s)
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1016/j.surg.2022.07.021
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ライセンス | http://creativecommons.org/licenses/by-nc-nd/4.0/
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助成機関名 |
Japan Society for the Promotion of Science
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助成番号 | 20K22953
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