@techreport{oai:ir.kagoshima-u.ac.jp:00010645,
 author = {佐原, 寿史},
 month = {2016-10-28},
 note = {2009-2010年度科学研究費補助金(若手研究(B))研究成果報告書 課題番号：21791322　研究代表者：佐原寿史 (鹿児島大学フロンティアサイエンス研究推進センター特任准教授 (※課題採択時は京都大学・医学(系)研究科(研究院)・助教)), 一酸化炭素（CO）のもつ強力な細胞臓器保護作用は移植医療での有効な治療となりうるが、有毒ガスとして知られるCOの臨床応用には大動物による検討が必須と考え、MHC確立クラウン系ミニブタを用いた肺移植実験に着手した。移植時のドナー180分およびレシピエント390分の低濃度CO吸入が、副作用を生ずることなく、MHC完全不適合移植肺の生存延長効果を有した。更にドナーへのCO吸入のみでも同様の効果が得られた。前臨床大動物実験で得られたこれらの結果は、副作用の懸念が少ない臨床応用性の高いCOを用いた新たな治療法の確立に重要な知見である。, Carbon monoxide (CO) is produced endogenously as a byproduct of heme catalysis, and has been shown to provide protection against ischemia-reperfusion injury (IRI) in a variety of organs in murine models. Since CO is also known to be a toxic gas, translational research using large animals is essential prior to its use in the clinic. To attempt CO to apply for the clinical setting, we examined whether (1) perioperative CO inhalation to both donor and recipient prolongs lung graft survival (2) donor treatment alone is sufficient to prolong graft survival and (2) postoperative CO therapy has additional survival benefits in MHC-inbred CLAWN miniature swine. Eighteen CLAWN swine received fully MHC mismatched lungs with 12 days of tacrolimus (days 0-11; 35-45 ng/ml). In Group 1 (n=6), recipients received tacrolimus alone. In Group 2 (n=5), both donors and recipients inhaled 200-250 ppm CO (180 min for donors; 390 min for recipients until 2-hr reperfusion). In Group 3 (n=4), only donors were treated with CO for 180 min. In Group 4 (n=3), recipients were additionally given daily 1-hour 250 ppm CO for 14 postoperative days. All recipients in Group 1 uniformly rejected their grafts by postoperative day 63 with development of cytotoxic antidonor antibodies. In contrast, 4 out of 5 recipients in Group 2 accepted their grafts beyond 63 days. Short-term CO treatment only with donor (Group 3) was effective in prolonging allograft survival. Three out of 4 recipients accepted their grafts beyond 63 days with the longest survivor lasting 150 days. In Group 4, two out of 3 recipients maintained their grafts for 91 days; however, postoperative CO did not prolong graft survival compared to Group 2. Development of antidonor-antibodies and donor-specific responsiveness by MLR and CML assays was delayed in animals that received CO therapy. Furthermore, fewer inflammatory cell infiltrates and injuries of endothelial cells were seen on POD2 biopsies, and serum concentrations of the pro-inflammatory cytokines (IL-1β, IL-6) also decreased in Group 2-4. These data suggest that donor CO treatment alone is sufficient to improve lung allograft survival in a clinically relevant large animal model. Donor cytoprotective preconditioning with CO during organ harvest or preservation could be accomplished in a clinical setting, potentially improving graft survival with little risk of adverse effects on the recipient.},
 title = {移植肺生存向上とドナー数拡大を目指す一酸化炭素療法の大動物肺移植モデルによる検討},
 year = {}
}