2002 Fiscal Year Annual Research Report

妊娠中毒症における血管内皮障害及び障害修復に関する研究

Research Project

Project/Area Number	13770919
Research Institution	Okayama University
Principal Investigator	野口聡一岡山大学, 医学部附属病院, 助手 (10322231)
Keywords	preeclampsia / nitric oxide / oxidative stress / endothelial dysfunction
Research Abstract	[目的]妊娠中毒症では血管機能障害が病態形成に重要な役割を果たしていると考えられる.今回私達は,重症妊娠中毒症妊婦血清の血管内皮細胞に対する傷害作用・修復阻害作用を検討した. [方法]妊娠28〜32週の正常妊婦または重症妊娠中毒症妊婦(各n=7)の静脈血を同意のもと採取し,血清分離後-40℃に保存した.マウス血管内皮細胞株(MSS31)の培地に各検体血清を最終濃度10%になるように添加し24〜48時間培養し影響を検討した.細胞増殖はtrypan blue dye exhaust testにて,cell migrationはwound healing assayにて測定した.一酸化窒素(NO)産生は培養液中のnitrite濃度で,peroxynitriteの産生は抗nitrotyrosine抗体を用いたdot blotで評価した.内皮型NO産生酵素(eNOS),誘導型NO産生酵素(iNOS)の発現はimmunoblottingで検討した.またマクロアレイ法により血管新生に関与するmRNA発現の違いを検討した. [成績]重症妊娠中毒症妊婦血清添加後24時間では正常妊婦血清添加に比し,NO産生は有意に亢進し,iNOS発現亢進,eNOSの発現低下が認められ,peroxynitrite産生はやや亢進した.細胞増殖及びcell migrationは抑制されたが,VEGF等の血管新生に関与する増殖因子のmRNA発現は亢進した.細胞増殖・cell migrationは血清添加48時間では重症妊娠中毒症と正常妊婦血清の間の有意差が無くなったが,培地を24時間毎に変更した場合は24時間同様,中毒症血清添加で有意に抑制された. [結論]重症妊娠中毒症妊婦血清添加24時間では細胞増殖・cell migrationは抑制されたことより,重症妊娠中毒症血清には血管内皮障害作用があると考えられる.またVEGF等の増殖因子の発現亢進も妊娠中毒症病態形成に何らかの影響を及ぼしている可能性があると思われる.

Research Products
(8 results)

All Other

All Publications (8 results)

[Publications] Soichi Noguchi, Mikiya Nakatsuka, Kazuo Asagiri, et al.: "Nafamostat mesilate, a serine protease inhibitor, suppresses NF-κB mediated induction of NO synthase in lipopolysaccharide-treated macrophages"International Immunopharmacology. (in press). (2003)
[Publications] Soichi Noguchi, Mikiya Nakatsuka, Kazuo Asagiri, et al.: "Bisphenol A stimulates NO synthesis through a non-genomic estrogen receptor-mediated mechanism in mouse endothelial cells"Toxicology Letters. 135. 95-101 (2002)
[Publications] 野口聡一, 中塚幹也, 鎌田泰彦, 他: "重症妊娠中毒症妊婦血清の血管内皮細胞への作用"日本妊娠中毒症学会雑誌. 10. 99-100 (2002)
[Publications] Kazuo Asagiri, Mikiya Nakatsuka, Hideki Konishi, Soichi Noguchi, et al.: "Involvement of peroxynitrite in LPS-induced apoptosis of trophoblasts"The Journal of Obstetrics and Gynecology Research. 29. 49-55 (2003)
[Publications] Nakatsuka M, Habara T, Noguchi S, et al.: "Impaired uterine arterialblood flow in pregnant women with recurrent pregnancy loss"Journal of Ultrasound in Medicine. 22. 27-31 (2003)
[Publications] Mikiya Nakatsuka, Masayo Takata, Katsuhiko Tada, Kazuo Asagiri, Toshihiro Habara, Soichi Noguchi, et al.: "A Long-term Transdermal Nitric Oxide Donor Improves Uteroplacental Circulation in Women With Preeclampsia"Journal of Ultrasound in Medicine. 21. 831-836 (2002)
[Publications] Habara T, Nakatsuka M, Konishi H, Asagiri K, Noguchi S, Kudo T: "Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss"Human Reproduction. 17. 190-194 (2002)
[Publications] Chebib Chekir, 中塚幹也, 野口聡一, 他: "妊娠中毒症,SLE胎盤におけるAdvanced glycation end products(AGEs)蓄積と障害"日本妊娠中毒症学会雑誌. 10. 111-112 (2002)

2002 Fiscal Year Annual Research Report

妊娠中毒症における血管内皮障害及び障害修復に関する研究

Principal Investigator

野口 聡一 岡山大学, 医学部附属病院, 助手 (10322231)

Research Products

[Publications] Soichi Noguchi, Mikiya Nakatsuka, Kazuo Asagiri, et al.: "Nafamostat mesilate, a serine protease inhibitor, suppresses NF-κB mediated induction of NO synthase in lipopolysaccharide-treated macrophages"International Immunopharmacology. (in press). (2003)

[Publications] Soichi Noguchi, Mikiya Nakatsuka, Kazuo Asagiri, et al.: "Bisphenol A stimulates NO synthesis through a non-genomic estrogen receptor-mediated mechanism in mouse endothelial cells"Toxicology Letters. 135. 95-101 (2002)

[Publications] 野口聡一, 中塚幹也, 鎌田泰彦, 他: "重症妊娠中毒症妊婦血清の血管内皮細胞への作用"日本妊娠中毒症学会雑誌. 10. 99-100 (2002)

[Publications] Kazuo Asagiri, Mikiya Nakatsuka, Hideki Konishi, Soichi Noguchi, et al.: "Involvement of peroxynitrite in LPS-induced apoptosis of trophoblasts"The Journal of Obstetrics and Gynecology Research. 29. 49-55 (2003)

[Publications] Nakatsuka M, Habara T, Noguchi S, et al.: "Impaired uterine arterialblood flow in pregnant women with recurrent pregnancy loss"Journal of Ultrasound in Medicine. 22. 27-31 (2003)

[Publications] Mikiya Nakatsuka, Masayo Takata, Katsuhiko Tada, Kazuo Asagiri, Toshihiro Habara, Soichi Noguchi, et al.: "A Long-term Transdermal Nitric Oxide Donor Improves Uteroplacental Circulation in Women With Preeclampsia"Journal of Ultrasound in Medicine. 21. 831-836 (2002)

[Publications] Habara T, Nakatsuka M, Konishi H, Asagiri K, Noguchi S, Kudo T: "Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss"Human Reproduction. 17. 190-194 (2002)

[Publications] Chebib Chekir, 中塚幹也, 野口聡一, 他: "妊娠中毒症,SLE胎盤におけるAdvanced glycation end products(AGEs)蓄積と障害"日本妊娠中毒症学会雑誌. 10. 111-112 (2002)

野口聡一岡山大学, 医学部附属病院, 助手 (10322231)