Biochemical and Molecular Biological Investigation of the Pregnancy Associated Uterine Blood Flow Increase-As a Basic Study for Developing Future Treatment of Intrauterine Growth Retardation-

妊娠相关子宫血流量增加的生化和分子生物学研究-作为开发未来宫内生长迟缓治疗的基础研究-

• 批准号: 11671611
• 负责人: ITOH Hiroaki
• 金额: $ 2.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671611/
• 关键词: pregnancy; uterine artery; nitric oxide; cGMP; CNP; Nitric Oxide; nitric oxide(NO); prostacyclin; estorgen receptor

Pregnancy increases uterine artery blood flow approximately 30 fold for supply oxygen and nutrition to developing fetus, the physiological mechanism of which has not been fully clarified. Recently, pulsed Doppler ultrasound investigations suggested a possibility that this physiological increase of uterine blood flow was disturbed in some cases of intrauterine growth retardation (IUGR). Therefore, the aim of the study is to investigate, the possible involvement of two major guanylate cyclase systems, nitric oxide (NO) / soluble gaunylate system (sGC) andC-type natriuretic peptide (CNP) / particulate guanylate cyclase-B (GC-B) system, in the regulation of uterine artery blood flow during pregnancy.In this study we revealed that pregnancy increased the protein and mRNA expression of endothelial NO synthase (eNOS), sGC, CNP and GC-B increased in uterine artery, but not renal nor omental arteries from pregnant sheep. The in vitro enzyme activities of both sGC and GC-B, estimated by cGMP pro … More duction, in the tissues of uterine arteries from pregnant sheep was significantly higher than those renal or omental arteries. This local up-regulation of cGMP generation in uterine artery was not observed in nonpregnant sheep. Thus, both NO/sGC and CNP/GC-B pathways were specifically up-regulated in ovine uterine artery during pregnancy, contributing to uterine artery blood flow increase by augmenting local cGMP generation.Moreover, the plasma cGMP concentrations in normal pregnant women were significantly elevated during pregnancy, which suggested a possibility that the up-regulation of guanylate cyclate system might be also involved in human uterine artery blood flow increase during pregnancy. The plasma cGMP concentrations in mild preeclampsia pregnant women were significantly higher than those in severe preeclampsia, for all maternal severe hyper tension as well as complication with IUGR.These data all together suggested an interesting possibility that the preganacy associated up-regulation of systemic and/or local guanylate cyclase system might be deteriorated in cases of maternal severe preeclampsia. Less

怀孕时子宫动脉血流量增加约30倍，为发育中的胎儿提供氧气和营养，其生理机制尚未完全阐明。最近，脉冲多普勒超声研究表明，在某些宫内生长迟缓（IUGR）病例中，子宫血流的这种生理性增加可能受到干扰。因此，本研究的目的是探讨两种主要鸟苷酸环化酶系统，即一氧化氮（NO）/可溶性鸟苷酸环化酶系统（sGC）和C型利钠肽（CNP）/颗粒鸟苷酸环化酶-B（GC-B）系统在妊娠期间子宫动脉血流的调节中的可能参与。 怀孕绵羊子宫动脉中内皮一氧化氮合酶 (eNOS)、sGC、CNP 和 GC-B 的 mRNA 表达增加，但肾动脉和网膜动脉中则没有增加。根据 cGMP 产生估计，怀孕羊子宫动脉组织中 sGC 和 GC-B 的体外酶活性显着高于肾动脉或大网膜动脉。在未怀孕的绵羊中没有观察到子宫动脉中 cGMP 产生的局部上调。因此，NO/sGC和CNP/GC-B通路在妊娠期间在绵羊子宫动脉中特异性上调，通过增加局部cGMP生成而导致子宫动脉血流量增加。此外，正常孕妇的血浆cGMP浓度在妊娠期间显着升高，这表明鸟苷酸环化物系统的上调可能也参与了人类子宫 怀孕期间动脉血流量增加。对于所有患有严重高血压以及IUGR并发症的孕妇，轻度子痫前期孕妇的血浆cGMP浓度显着高于重度子痫前期孕妇。这些数据共同表明了一个有趣的可能性，即在孕妇严重子痫前期的情况下，与妊娠相关的全身和/或局部鸟苷酸环化酶系统的上调可能会恶化。较少的

项目成果

KK Okumura,N Sagawa,H Itoh, 他6名: "Platelet activating factor-acetyl hydrolase activity and nitric oxide metabolite level in plasma of pregnant women who developed transient hypertension later during pregnancy"Reprod Fertil Dev. 11(In Press). (2000)

KK Okumura、N Sakawa、H Itoh 和其他 6 人：“妊娠后期出现短暂性高血压的孕妇血浆中的血小板激活因子乙酰水解酶活性和一氧化氮代谢物水平”Reprod Fertil Dev 11（出版中）。 ）

H Itoh, et al.: "Role of the guanylate cyclase system in the regulation of ovine uterine arterial blood flow during pregnancy, a review"Trophoblast Research. 13. 301-309 (1999)

H Itoh 等人：“鸟苷酸环化酶系统在妊娠期间调节绵羊子宫动脉血流中的作用，综述”滋养层研究。

KK Okumura,H Itoh, 他6名: "Platelet activating factor-acetylhydrolase activity and nitric oxide metabolite level in plasma of pregnant women who developed transient hypertension later during pregnancy."Reprod Fertil Dev. 11. 75-79 (1999)

KK Okumura、H Itoh 和其他 6 人：“妊娠后期出现暂时性高血压的孕妇血浆中的血小板激活因子乙酰水解酶活性和一氧化氮代谢物水平。”Reprod Fertil Dev. 11. 75-79 (1999)

S Yura,H Itoh, 他7名: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest. 105. 749-755 (2000)

S Yura、H Itoh 和其他 7 人：“过度表达瘦素的雌性转基因瘦小鼠加速青春期和迟发性下丘脑性腺功能减退症。”J Clin Invest. 105. 749-755 (2000)

N Sagawa, H Itoh, et al.: "leptin as a novel placenta-derived hormone in humans."Trophoblast Research. 13. 25-34 (1999)

N Sakawa、H Itoh 等人：“瘦素作为人类中一种新型胎盘源性激素。”滋养层研究。