1997 年度実績報告書

NO消去剤の抗ショック治療への応用

研究課題

研究課題/領域番号	09557127
研究機関	熊本大学
研究代表者	前田浩熊本大学, 医学部, 教授 (90004613)
研究分担者	澤智裕熊本大学, 医学部, 助手 (30284756) 赤池孝章熊本大学, 医学部, 助教授 (20231798)
キーワード	NO / エンドトキシンショック / NO消去剤
研究概要	本年度の研究においては、NO消去剤であるPTIO(2-phenyl-4,4,5,5-tetramethyl-1-oxyl 3-oxide)の生体内における安定性とNO消去活性を改善させるため、PTIOのリポソーム製剤化を行った。その結果、飽和脂肪酸よりなるdistearoylphosphatidylcholineおよびdistearoylphosphatidylglycerolにcholesterolを添加し、エクスロルージョン法により0.2μmサイズのリポソームPTIOを作製した。本リポソーム製剤は、調節後も一ヶ月間点度安定で冷所保存でき、NO消去活性もほとんど失わない。また、ラットに静脈内投与しても、microembolizationなどをもたらすことなく、血中半減期もPTIOより著名に改善した。リポソームPTIOは、NOS合成阻害剤に認められる様な血圧上昇作用もなく、生体内において過剰なNOお消去することがわかった。さらに興味あることに、リポソームPTIOはNOをニトロソチオール(RS-NO)に変換し、正常なEDRFを損なわないことも明らかとなった。一方近年、ショック病態においてNO由来のニトロソチオールが末梢循環不全を改善させ、防御的に作用しているという報告もある。そこで現在我々は、リポソームPTIOによるNO消去とともに我々が最近作製した安定なニトロソ蛋白をショックモデルに投与し、その治療効果について検討を進めている。

研究成果
(16件)

すべてその他

すべて文献書誌 (16件)

[文献書誌] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : Implications for the treatment of multiple sclerosis" Proc. Natl. Acad. Sci. U.S.A. 94. 2528-2533 (1997)
[文献書誌] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)
[文献書誌] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 261-274 (1997)
[文献書誌] K. Kojima, et al.: "Development of a fluorescent indicator for bioimaging of nitric oxide" Biol. Pharm. Bull.20. 1229-1232 (1997)
[文献書誌] K. Sato, et al.: "Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea" Jpn. J. Cancer Res.88. 1199-1204 (1997)
[文献書誌] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1997)
[文献書誌] M. Yoshida, et al.: "Effect of the NO scavenger carboxy-PTIO on endothelium-dependent vasorelaxation of various blood vessels from rabbits" Life Sciences. 62. 203-211 (1998)
[文献書誌] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist" Infect. Immun.66. 866-869 (1998)
[文献書誌] K. Sato, et al.: "Therapeutic effet of erythromycin on influenza virus-induced lung injury in mice." Am. J. Respir. Crit. Care Med.(in press). (1998)
[文献書誌] H. Maeda, and T. Akaike: "Nitric oxide and oxygen radicals in infection, inflammation and cancer" Biochemistry (Moscow). (in press). (1998)
[文献書誌] H. Maeda, and T. Akaike: "Protease Inhibitors : Novel Therapeutic Application and Development (ed. N. Marcready)" International Business Communications, Inc., southborough, 33 (1997)
[文献書誌] H. Maeda, and T. Akaike: "Nitric Oxide in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell(in press), (1998)
[文献書誌] S. Tayama, et al.: "The Biology of Nitric Oxide Part6(eds. S. Moncada, N. Toda, H. Maeda and E.A. Higgs)" Portland Press, London(in press), (1998)
[文献書誌] E. Akizuki, et al.: "The Biology of Nitric Oxide Part6(eds. S. Moncada, N. Toda, H. Maeda and E.A. Higgs)" Portland Press, London(in press), (1998)
[文献書誌] T. Akaike and H. Maeda: "Nitric Oxide and Infection (ed. F.C. Fang)" Plenum Publishing Co., New York (in press), (1998)
[文献書誌] T. Akaike and Y. Miyamoto: "Experimental Protocols for Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) (eds. N. Taniguchi and J.M.C. Gutteridge)" Oxford University Press, New York, Oxford(in press), (1998)

1997 年度 実績報告書

NO消去剤の抗ショック治療への応用

研究代表者

前田 浩 熊本大学, 医学部, 教授 (90004613)

研究成果

[文献書誌] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : Implications for the treatment of multiple sclerosis" Proc. Natl. Acad. Sci. U.S.A. 94. 2528-2533 (1997)

[文献書誌] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)

[文献書誌] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 261-274 (1997)

[文献書誌] K. Kojima, et al.: "Development of a fluorescent indicator for bioimaging of nitric oxide" Biol. Pharm. Bull.20. 1229-1232 (1997)

[文献書誌] K. Sato, et al.: "Nitric oxide generation from hydroxyurea via copper-catalyzed peroxidation and implications for pharmacological actions of hydroxyurea" Jpn. J. Cancer Res.88. 1199-1204 (1997)

[文献書誌] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1997)

[文献書誌] M. Yoshida, et al.: "Effect of the NO scavenger carboxy-PTIO on endothelium-dependent vasorelaxation of various blood vessels from rabbits" Life Sciences. 62. 203-211 (1998)

[文献書誌] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist" Infect. Immun.66. 866-869 (1998)

[文献書誌] K. Sato, et al.: "Therapeutic effet of erythromycin on influenza virus-induced lung injury in mice." Am. J. Respir. Crit. Care Med.(in press). (1998)

[文献書誌] H. Maeda, and T. Akaike: "Nitric oxide and oxygen radicals in infection, inflammation and cancer" Biochemistry (Moscow). (in press). (1998)

[文献書誌] H. Maeda, and T. Akaike: "Protease Inhibitors : Novel Therapeutic Application and Development (ed. N. Marcready)" International Business Communications, Inc., southborough, 33 (1997)

[文献書誌] H. Maeda, and T. Akaike: "Nitric Oxide in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell(in press), (1998)

[文献書誌] S. Tayama, et al.: "The Biology of Nitric Oxide Part6(eds. S. Moncada, N. Toda, H. Maeda and E.A. Higgs)" Portland Press, London(in press), (1998)

[文献書誌] E. Akizuki, et al.: "The Biology of Nitric Oxide Part6(eds. S. Moncada, N. Toda, H. Maeda and E.A. Higgs)" Portland Press, London(in press), (1998)

[文献書誌] T. Akaike and H. Maeda: "Nitric Oxide and Infection (ed. F.C. Fang)" Plenum Publishing Co., New York (in press), (1998)

[文献書誌] T. Akaike and Y. Miyamoto: "Experimental Protocols for Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) (eds. N. Taniguchi and J.M.C. Gutteridge)" Oxford University Press, New York, Oxford(in press), (1998)

1997 年度実績報告書

前田浩熊本大学, 医学部, 教授 (90004613)