1999 Fiscal Year Annual Research Report

延髄孤束核へ一酸化窒素合成酵素のアンチセンスDNA導入による循環調節への効果

Research Project

Project/Area Number	10670074
Research Institution	University of Occupational and Environmental Health
Principal Investigator	前田正信産業医科大学, 産業生態科学研究所, 助教授 (80181593)
Co-Investigator(Kenkyū-buntansha)	平野英保産業医科大学, 医学部, 講師 (50040241)
Keywords	孤束核 / 一酸化窒素 / 一酸化窒素合成酵素 / アンチセンス / オリゴヌクレオチド / 脳 / 循環 / 遺伝子
Research Abstract	自然発症高血圧ラット(SHR)の高血圧発症のメカニズムを調べるため、延髄孤束核(nucleus tractus solitarius,NTS)に神経型一酸化窒素合成酵素(neuronal nitric oxide synthase,nNOS)のantisense oligodeoxynucleotide(ODN)を両側性に注入し、SHRのNTS内でのnNOSの発現を遺伝子レベルで抑制し、血圧・心拍数等の変化を観察した。また、その結果をSHRとWistar-Kyotoラット(WKY)で比較検討した。 1.nNOSアンチセンスODNsをSHRの両側NTSへの微量注入し(20 pmole/50 nl,n=8)、平均血圧の変化を観察すると、15分後にセンス(p<0.01,n=7)およびmismatch ODNs(p<0.01,n=7)と比べ、30分後にmismatch ODNs(p<0.05)と比べ有意に平均血圧は上昇した。アンチセンスの注入15分後の平均血圧は、注入前と比べ136±8%(mean±SE)へと上昇した。 2.アンチセンスの微量注入後の心拍数は、センスおよびmismatcnの注入時と比べ有意な上昇を示さなかった。 3.SHRにおける血圧上昇反応は、WKYに比べ(30-60分後)早く出現した。また、SHRにおける血圧上昇反応は、WKYに比べその程度が大きかった。SHRにおける血圧上昇反応がWKYに比べ早く出現しのは、SHRのNTSにおけるnNOSの発現量がWKYでの発現量より多いことが関係するかも知れない。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Maeda,M.: "Injection of antisense oligos to nNOS into nucleus tractus solitarii increases blood pressure"NeuroReport. 10(9). 1957-1960 (1999)
[Publications] Maeda,M.: "Central control mechanisms of circulation in the medulla oblongate by nitric oxide"Japanese Journal of Physiology,. 49(6). 467-478 (1999)
[Publications] Nakai,M.: "Scopolamine-sensitive and resistant components of increase in cerebral cortical blood flow elicited by periaqueductal gray matter of rats"Neuroscience Letters. 270(3). 173-176 (1999)
[Publications] Maeda,M.: "Increases in arterial blood pressure and heart rate produced by microinjection of antisense nNOS oligonucleotide into the nucleus tractus solitarii"Excerpta Medica International Congress Series. 1185 Neurology. 293-295 (1999)
[Publications] Inoue,M.: "Regional blood flow during activation of the nucleus tractus solitarius"Excerpta Medica International Congress Series. 1185 Neurology. 301-303 (1999)
[Publications] Nagata,S.: "Effects of anterior hypothalamic lesioning on late asthmatic response"Excerpta Medica International Congress Series,. 1185 Neurology. 315-317 (1999)
[Publications] Washio,M.: "The isolation of Methicillin-resistant Staphylococcus aureus (MRSA)is a predictor for poor prognosis of the elderly patients with bacterial infection"International Medical Journal. (in press 2000). (2000)
[Publications] Tsurudome,Y.: "Changes in levels of 8-hydroxyguanine in DNA,its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles"Carcinogenesis. 20. 1573-1576 (1999)
[Publications] Ohmori,O.: "Shifted cytosolic NADP+-dependent isocitrate dehydrogenase on 2-D gel in the brain of genetically epileptic E1 mice"Neurochem Res Mar. 24(3). 365-369 (1999)
[Publications] Aso,M.: "cDNA Cloning of Inducer Reactive Protein in Adult T-Cell Leukemia Cell by Applying to The Fuzzy Set Cloning Theory for Sequencing Defuzzification."Biomedical Soft Computing and Human Sciences. 5. 15-20 (1999)
[Publications] Yan,Y.: "The Occurrence of Polymorphism of Mannose 6-phosphate Insulin-like Growth Factor2 Receptor Gene in Laboratory and Wild Rats."J.UOEH. 21. 199-208 (1999)
[Publications] Arai,A.: "Detection of Mononuclear Cells as the Source of the Increased Tissue Factor mRNA in the Liver from Lipopolysaccharide-Treated Rats."Thrombosis Res. (in press). (1999)
[Publications] Tamura,M.: "Expression of Profilin,an Actin-binding Protein,in Rat Experimental Glomerulonephritis and its Upregulation by Basic Fibroblast Growth Factor in Cultured Rat Mesangial Cells"J Am Soc Nephrol. (in press). (2000)
[Publications] 中井正継: "大脳皮質非特殊活動-血流量カプリングを実現する伝達物質と機序"脳循環代謝. 10(4). 358-359 (1999)
[Publications] 平野英保: "ファジィ推論法によるアンチセンスの設計とその効果"バイオメディカル・ファジィ・システム学会1999年2月九州地方学会学術集会論文集,. 6. 3-4 (1999)
[Publications] 平野英保: "PCRやRT-PCRやアンチセンスオリゴヌクレオタイドのファジィ推論による設計と組織培養細胞やラットに対する効果"バイオメディカル・ファジィ・システム学会大12回年次大会講演論文集,. 12. 87-90 (1999)
[Publications] 前田正信: "各国の労働安全衛生関連法規・制度の国際比較-主に産業医倫理に関して-(総説)"産業衛生学雑誌. 41(3). 45-53 (1999)
[Publications] 前田正信: "アンチセンス法を用いて延髄孤束核のnNOSの遺伝子を制御した時の循環変化"自律神経. (in press). (2000)
[Publications] Hirano,H.: "Application to Malignant Tumor Cells for Fuzzy Set Chaos Theory During.Histological Regulation to Envelope.In Proceedings of Internatio.Symp.Med.Informatics & Fuzzy Techno."In Proceedings of Internatio.Symp.Med.Informatics & Fuzzy Techno.edited by Arita S,. 8 (1999)
[Publications] Maeda,M.: "International comparison of periodic health examination and midecal privacy of workers.In Proceedings of the 19th UOEH and the 3rd IIES International Symposium.Periodic Health Examination for Workers:What should be done for the improvement?"In Proceedings of the 19th UOEH and the 3rd IIES International Symposium.Periodic Health Examination for Workers:What should be done for the improvement?(in press). (2000)
[Publications] Inoue,M.: "Effects of different work styles.on blood pressure.In Proceedings of the 19th UOEH and the 3rd IIES International Symposium.Periodic Health Examination for Workers:What should be done for the improvement?"In Proceedings of the 19th UOEH and the 3rd IIES International Symposium.Periodic Health Examination for Workers:What should be done for the improvement?(in press). (2000)

1999 Fiscal Year Annual Research Report

延髄孤束核へ一酸化窒素合成酵素のアンチセンスDNA導入による循環調節への効果

Principal Investigator

前田 正信 産業医科大学, 産業生態科学研究所, 助教授 (80181593)

Research Products

[Publications] Maeda,M.: "Injection of antisense oligos to nNOS into nucleus tractus solitarii increases blood pressure"NeuroReport. 10(9). 1957-1960 (1999)

[Publications] Maeda,M.: "Central control mechanisms of circulation in the medulla oblongate by nitric oxide"Japanese Journal of Physiology,. 49(6). 467-478 (1999)

[Publications] Nakai,M.: "Scopolamine-sensitive and resistant components of increase in cerebral cortical blood flow elicited by periaqueductal gray matter of rats"Neuroscience Letters. 270(3). 173-176 (1999)

[Publications] Maeda,M.: "Increases in arterial blood pressure and heart rate produced by microinjection of antisense nNOS oligonucleotide into the nucleus tractus solitarii"Excerpta Medica International Congress Series. 1185 Neurology. 293-295 (1999)

[Publications] Inoue,M.: "Regional blood flow during activation of the nucleus tractus solitarius"Excerpta Medica International Congress Series. 1185 Neurology. 301-303 (1999)

[Publications] Nagata,S.: "Effects of anterior hypothalamic lesioning on late asthmatic response"Excerpta Medica International Congress Series,. 1185 Neurology. 315-317 (1999)

[Publications] Washio,M.: "The isolation of Methicillin-resistant Staphylococcus aureus (MRSA)is a predictor for poor prognosis of the elderly patients with bacterial infection"International Medical Journal. (in press 2000). (2000)

[Publications] Tsurudome,Y.: "Changes in levels of 8-hydroxyguanine in DNA,its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles"Carcinogenesis. 20. 1573-1576 (1999)

[Publications] Ohmori,O.: "Shifted cytosolic NADP+-dependent isocitrate dehydrogenase on 2-D gel in the brain of genetically epileptic E1 mice"Neurochem Res Mar. 24(3). 365-369 (1999)

[Publications] Aso,M.: "cDNA Cloning of Inducer Reactive Protein in Adult T-Cell Leukemia Cell by Applying to The Fuzzy Set Cloning Theory for Sequencing Defuzzification."Biomedical Soft Computing and Human Sciences. 5. 15-20 (1999)

[Publications] Yan,Y.: "The Occurrence of Polymorphism of Mannose 6-phosphate Insulin-like Growth Factor2 Receptor Gene in Laboratory and Wild Rats."J.UOEH. 21. 199-208 (1999)

[Publications] Arai,A.: "Detection of Mononuclear Cells as the Source of the Increased Tissue Factor mRNA in the Liver from Lipopolysaccharide-Treated Rats."Thrombosis Res. (in press). (1999)

[Publications] Tamura,M.: "Expression of Profilin,an Actin-binding Protein,in Rat Experimental Glomerulonephritis and its Upregulation by Basic Fibroblast Growth Factor in Cultured Rat Mesangial Cells"J Am Soc Nephrol. (in press). (2000)

[Publications] 中井正継: "大脳皮質非特殊活動-血流量カプリングを実現する伝達物質と機序"脳循環代謝. 10(4). 358-359 (1999)

[Publications] 平野英保: "ファジィ推論法によるアンチセンスの設計とその効果"バイオメディカル・ファジィ・システム学会1999年2月九州地方学会学術集会論文集,. 6. 3-4 (1999)

[Publications] 平野英保: "PCRやRT-PCRやアンチセンスオリゴヌクレオタイドのファジィ推論による設計と組織培養細胞やラットに対する効果"バイオメディカル・ファジィ・システム学会大12回年次大会講演論文集,. 12. 87-90 (1999)

[Publications] 前田正信: "各国の労働安全衛生関連法規・制度の国際比較-主に産業医倫理に関して-(総説)"産業衛生学雑誌. 41(3). 45-53 (1999)

[Publications] 前田正信: "アンチセンス法を用いて延髄孤束核のnNOSの遺伝子を制御した時の循環変化"自律神経. (in press). (2000)

[Publications] Hirano,H.: "Application to Malignant Tumor Cells for Fuzzy Set Chaos Theory During.Histological Regulation to Envelope.In Proceedings of Internatio.Symp.Med.Informatics & Fuzzy Techno."In Proceedings of Internatio.Symp.Med.Informatics & Fuzzy Techno.edited by Arita S,. 8 (1999)

前田正信産業医科大学, 産業生態科学研究所, 助教授 (80181593)