@article{oai:twinkle.repo.nii.ac.jp:00017752,
 author = {SUGA, Hiroyasu and NAKAGAWA, Takao and MIYOSHI, Norio and IMAMURA, Yoshiaki and FUKUDA, Masaru},
 issue = {3},
 journal = {東京女子医科大学雑誌},
 month = {Mar},
 note = {先に,ラットにおいて出血性侵襲後のDICの発症を確認し,その際組織一酸化窒素(NO)産生の早期の増加を認めた.これは,NO産生の増加はDICの早期診断の指標としての可能性を示唆した.今回の研究では,ラットにおける出血性侵襲後の組織NO産生を,エンドトキシン適用後のラットと比較しながら検討した.Pentobarbital麻酔下のラットを用いた.開腹の後,腎にNO選択性電極を設置して組織NO産生をリアルタイムで記録した.ラットにおいて出血性侵襲(推定全血量の30%量の放血)およびエンドトキシン投与(LPS, E. coli, 10mg/kgiv)により,凝固線溶系,血中サイトカインレベルおよび組織病理学的所見から,DICの発症を確認した.出血性侵襲後のNO産生は,早期(侵襲後1hr以内)に速やかに増加してピークに達した.これに対し,エンドトキシン投与後のNO産生は,早期には全く認められず,2～3hr後より緩徐な増加が認められるようになり,4～6hr後にピークに達した.出血性侵襲およびエンドトキシン投与後のN-(dithiocarboxy) sarcosine, disodiumsalt, dihydrate (DTCSNa)を用いた電子スピン共鳴スペクトラム分析(ESR)によりNO-Fe-DTCSのシグナルを検出した.出血性侵襲による早期のN0産生は選択的iNOS阻害剤S-methylisothiourea (SMT, 5mg/kgiv)では殆ど影響をうけず,非選択的NOS阻害剤N^G-monomethyl-L-arginine (L-NMMA, 50mg/kgiv)により抑制され,cNOSの活性化によるものであり,iNOSの関与のないことが強く示唆された.これに対し,エンドトキシン投与による後期のNO産生はSMTおよびL-NMMAの添加により抑制され,主としてiNOSの誘導によることが強く示唆された.かくして,出血性侵襲およびエンドトキシン適用後の組織NO産生の過程の差異が確認された.これらとDICの病態との詳細な関連性は今後の検討に残されている., Previouly we confirmed the onset of DIC following hemorrhagic invasion in the rat, and at that time we noticed that nitric oxide (NO) production in the tissue increased rapidly and reached a peak in the early stage. This suggested that the increase in NO production would serve as an indicator for diagnosis of DIC. In the present study, we investigated the NO production in the tissue following hemorrhagic invasion in the rat, in comparsion with the rat following endotoxin administration. Rats under pentobarbital anesthesia were used. After laparotomy, NO-selective electrode was placed in the kidney for real time recording of NO production in the tissue. The onset of DIC following both hemorrhagic invasion (bleeding of 30% of the predetermined total blood volume) and endotoxin administration (LPS, E. coli, 10 mg/kg iv) was confirmed from the changes in the coagulation-fibrinolytic system, cytokine levels in the blood and histopathological findings. NO production in the tissue following hemorrhagic invasion increased rapidly and reached a peak within 1 hr after bleeding. On the contrary, NO production following endotoxin administration was not observed entirely at an early stage, but it began to increase gradually 2 to 3 hr after the administration and reached a peak after 4 to 6 hr. The electron spin resonance (ESR) analysis was performed on the kidney tissues from rats underwent hemorrhagic invasion or endotoxin administrations using N-(dithiocarboxy) sarcosine, disodium salt, hydrate (DTCS Na) as a NO trapping agent. These tissues showed typical ESR signal of NO-Fe-DTCS. NO production following hemorrhagic invasion was not affected by the selective iNOS inhibitor, S-methylisothiourea (SMT, 5 mg/kg iv), and inhibited by the non-selective NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA, 50 mg/kg iv), which strongly suggested that it was due to cNOS. On the contrary, NO production following endotoxin administration was inhibited clearly by SMT and L-NMMA, which strongly suggested that it was mainly due to iNOS. Thus, the difference in the processes of NO production in the tissue following hemorrhagic invasion and endotoxin administration were confirmed, while their correlation to pathological manifestations of DIC in detail is remained to investigate further.},
 pages = {80--91},
 title = {Comparison of Nitric Oxide (NO) Production in the Tissue Following Hemorrhagic Invasion and Endotoxin Administration in Rats in Relation to the Pathogenesis of Traumatic DIC},
 volume = {70},
 year = {2000}
}