2000 Fiscal Year Annual Research Report

誘導型NO合成酵素(iNOS)の抗動脈硬化作用-iNOSノックアウトマウスを用いて-

Research Project

Project/Area Number	11838018
Research Institution	Tokai University
Principal Investigator	中澤博江東海大学, 医学部, 教授 (20110885)
Co-Investigator(Kenkyū-buntansha)	一守康史東海大学, 医学部, 講師 (60184636) 石田英之東海大学, 医学部, 講師 (20222424)
Keywords	NO合成酵素 / nNOS / iNOS / eNOS / ノックアウト / LDL酸化 / マクロファージ
Research Abstract	12年度は、iNOSノックアウトマウス(iNOS^<-/->)と野生型マウス(C57BL/6、iNOS^<+/+>)の2群において、高脂肪食投与4ヶ月目に大動脈を採取し連続切片のHE染色、immunohistochemistry、iNOS蛋白とmRNA測定を行った。これにより下記の項目が明らかになった。 1)大動脈起始部に両群とも有意な動脈硬化巣が見られた。 2)硬化巣の面積は、iNOS^<-/->:285±73×10^3μm^2,n=10で、iNOS^<+/+>:293±82×10^3μm^2,n=10と両群で差がなかった。 3)大動脈のHomogenateではiNOS^<+/+>ではiNOSが誘導された(iNOS^<-/->では陰性)。これはmRNA、iNOS蛋白、iNOSの組織染色全てで示すことが出来た。 4)ニトロチロシン染色もiNOS^<+/+>のみ認め、iNOS染色陽性部と一致していた。 5)iNOSとニトロチロシンは主としてにマクロファージに認められた。 6)動脈硬化巣のコラーゲン染色によってiNOS^<+/+>ではiNOS^<-/->に比較しコラーゲン組織が有意に減少していた。コラーゲン線維の有無は動脈硬化巣の脆弱性を決める重要な因子である。コラーゲン線維の減少は、動脈硬化巣が破綻し易い事を示し、acute coronary syndrome(急性冠不全症候群)に結びつく事が分かっている。したがって、本研究の成果は、心筋梗塞の予防に関する臨床的にも有用な新知見である。今後の研究として、iNOSの誘導によって生じるコラーゲン線維の減少をきたすメカニズムを明らかにする必要性が示された。

Research Products

(9 results)

All Other

All Publications (9 results)

[Publications] Xi-Lin Niu: "Inducible nitric oxide synthase deficiency does not affect susceptibility of mice to atherosclerosis but increases collagen content in lesions."Circulation. (in press). (2000)
[Publications] Asahi K: "Nitric oxide inhibits the formation of advanced glycation end products."Kidney Int. 58. 1780-1787 (2000)
[Publications] Hirabayashi H: "Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusion."Brain Res. 852. 319-325 (2000)
[Publications] Niu Xi Lin: "Tanshinone II-A inhibits low density lipoprotein oxidation in viro."Free Rad Res. 33. 305-312 (2000)
[Publications] Hayashi Y: "P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production."J Thorac Cardiovasc Surg. 120. 558-565 (2000)
[Publications] Niu Xi-Lin: "Inducible Nitric Oxide Synthase knockout Mouse Macrophages Disclose Prooxidant Effect of Interferon-γ on Low-Density Lipoprotein Oxidation."Nitric Oxide : Biol and Chem. 4. 363-371 (2000)
[Publications] Tsuji C: "Nakazawa H : Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury."Am J Physiol Lung Cell Mol Physiol. 278. L719-L725 (2000)
[Publications] Hayashi Y: "MET-88, aγ-butyrobetain hydroxylase inhibitor improves cardiac SR Ca2+ uptake activity in rats with congestive heart failure following myocardial infarction."Mol Cell Biochem. 209. 39-46 (2000)
[Publications] Kato T: "Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats."Circ Res. 87. 937-945 (2000)

2000 Fiscal Year Annual Research Report

誘導型NO合成酵素(iNOS)の抗動脈硬化作用-iNOSノックアウトマウスを用いて-

Principal Investigator

中澤 博江 東海大学, 医学部, 教授 (20110885)

Research Products

[Publications] Xi-Lin Niu: "Inducible nitric oxide synthase deficiency does not affect susceptibility of mice to atherosclerosis but increases collagen content in lesions."Circulation. (in press). (2000)

[Publications] Asahi K: "Nitric oxide inhibits the formation of advanced glycation end products."Kidney Int. 58. 1780-1787 (2000)

[Publications] Hirabayashi H: "Nitrotyrosine generation via inducible nitric oxide synthase in vascular wall in focal ischemia-reperfusion."Brain Res. 852. 319-325 (2000)

[Publications] Niu Xi Lin: "Tanshinone II-A inhibits low density lipoprotein oxidation in viro."Free Rad Res. 33. 305-312 (2000)

[Publications] Hayashi Y: "P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production."J Thorac Cardiovasc Surg. 120. 558-565 (2000)

[Publications] Niu Xi-Lin: "Inducible Nitric Oxide Synthase knockout Mouse Macrophages Disclose Prooxidant Effect of Interferon-γ on Low-Density Lipoprotein Oxidation."Nitric Oxide : Biol and Chem. 4. 363-371 (2000)

[Publications] Tsuji C: "Nakazawa H : Increased production of nitrotyrosine in lung tissue of rats with radiation-induced acute lung injury."Am J Physiol Lung Cell Mol Physiol. 278. L719-L725 (2000)

[Publications] Hayashi Y: "MET-88, aγ-butyrobetain hydroxylase inhibitor improves cardiac SR Ca2+ uptake activity in rats with congestive heart failure following myocardial infarction."Mol Cell Biochem. 209. 39-46 (2000)

[Publications] Kato T: "Calmodulin kinases II and IV and calcineurin are involved in leukemia inhibitory factor-induced cardiac hypertrophy in rats."Circ Res. 87. 937-945 (2000)

中澤博江東海大学, 医学部, 教授 (20110885)