トキタ ダイスケ   TOKITA Daisuke
  時田 大輔
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model.
掲載誌名 正式名:American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
略  称:Am J Transplant
ISSNコード:16006143/16006135
掲載区分国外
巻・号・頁 12(11),pp.2938-48
著者・共著者 Sugimoto R, Okamoto T, Nakao A, Zhan J, Wang Y, Kohmoto J, Tokita D, Farver C F, Tarpey M M, Billiar T R, Gladwin M T, McCurry K R
発行年月 2012/11
概要 Ischemia/reperfusion injury (IRI) is the most common cause of early mortality following lung transplantation (LTx). We hypothesized that nitrite, an endogenous source of nitric oxide (NO), may protect lung grafts from IRI. Rat lung grafts were stored in preservation solution at 4°C for 6 hours. Both grafts and recipients were treated with nitrite. Nitrite treatment was associated with significantly higher levels of tissue oxygenation, lower levels of cytokines and neutrophil/macrophage infiltration, lower myeloperoxidase activity, reduced oxidative injury and increased cGMP levels in grafts than in the controls. Treatment with either a nitric oxide scavenger or a soluble guanylyl cyclase (sGC) inhibitor diminished the beneficial effects of nitrite and decreased cGMP concentrations. These results suggest that nitric oxide, generated from nitrite, is the molecule responsible for the effects of nitrite via the nitric oxide/sGC/cGMP pathway. Allopurinol, a xanthine oxidoreductase (XOR) inhibitor, abrogated the protective effects of nitrite, suggesting that XOR is a key enzyme in the conversion of nitrite to nitric oxide. In vitro experiments demonstrated that nitrite prevented apoptosis in pulmonary endothelial cells. Nitrite also exhibits longer survival rate in recipients than control. In conclusion, nitrite inhibits lung IRI following cold preservation and had higher survival rate in LTx model.
DOI 10.1111/j.1600-6143.2012.04169.x
PMID 23016570