Research for the perinatal adaptation of fetus and newborn ; relation to apoptosis and growth factor

胎儿和新生儿围产期适应研究；

• 批准号: 08671895
• 负责人: HIRAMATSU Yuji
• 金额: $ 1.41万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671895/
• 关键词: fetus; newborn; perinatal period; epidermal growth factor; polyamine; heme metabolism; diabetes mellitus; placenta; ポリアミン; DFMO; 胎児発育; EGF; Apoptosis; 糖代謝

Fetus and newborn show the many physiological and metabolic changes to adapt the dramatic environmental changes around the delivery. We investigated the hormones, growth factors and substances related to these changes.EGF increased fetal weight by controlling the amino acid transport in placenta. Retinol, insulin and insulin like growth factor also increased amino acid transport. EGF promoted the functional and morphological development of neonatal rat intestine and this change was inhibited by DL-α-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC).Inhibition of polyamine synthesis by DFMO also induced intrauterine growth restriction. The depression of ODC activity in the placenta is the major factor of IUGR induced by DEMO administration, and polyatnines play important roles to carry pregnancy.We investigated heme metabolism in placenta. Transcription levels of the non-specific δ-aminolevulinate synthase and heme oxygenase-1 in placenta at the terminal stage of pregnancy were increased markedly and these enzymes were exclusively expressed in the trophoblast. Both enzymes were influenced by acute fetal hypoxia and suggest that placental heme metabolism is influenced by the oxygen supply.We established a sireptozotocin (STZ)-treated pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. This model closely is useful for basic study of the pathophysiology of pregnancy with diabetes.These data suggest that many hormones, growth factors and substances such as EGF, polyamine, insulin, retinoids which related to cell growth play some important roll during the perinatal period.

胎儿和新生儿表现出许多生理和代谢变化，以适应分娩前后剧烈的环境变化。EGF通过调节胎盘中氨基酸的转运而增加胎儿体重。视黄醇、胰岛素和胰岛素样生长因子也增加氨基酸转运。EGF可促进新生大鼠小肠的功能和形态发育，这种作用可被不可逆的鸟氨酸脱羧酶（ODC）抑制剂DL-α-二氟甲基鸟氨酸（DFMO）所抑制，DFMO抑制多胺合成也可导致宫内生长受限。胎盘ODC活性降低是DEMO诱发IUGR的主要因素，而多胺在妊娠中起重要作用。妊娠晚期胎盘组织中非特异性δ-氨基乙酰丙酸合成酶和血红素加氧酶-1的转录水平显著升高，且仅在滋养层表达。这两种酶的影响，由急性胎儿缺氧，并建议，胎盘血红素代谢的影响，由oxygensupply.We建立了sireptozotocin（STZ）治疗的妊娠大鼠模型，糖尿病和体征和症状模仿先兆子痫。本模型为妊娠合并糖尿病的病理生理学基础研究提供了良好的实验依据，提示多种激素、生长因子以及与细胞生长有关的物质如EGF、多胺、胰岛素、维甲酸等在围产期起着重要作用。

项目成果

Nishii E, Hiramatsu Y, Ishida M, Nakata T, Ihara N, Odaka K, Kamimura S, Kudo T: "Effects of epidermal growth factor on neonetal intestinal development in rats"Proceeding of the 32nd Annual Congress of Jaoan Society of Neonatology. 207 (1996)

Nishii E、Hiramatsu Y、Ishida M、Nakata T、Ihara N、Odaka K、Kamimura S、Kudo T：“表皮生长因子对大鼠新生儿肠道发育的影响”Jaoan 新生儿学会第 32 届年会论文集。

Naomi Ihara, Reiko Akagi, Kohei Ejiri, Takafumi Kudo, Kazumichi Furuyama, Hiroyoshi Fujita: "Developmental changes of gene expression in heme metabolic enzymes in rat placenta"FEBS Letters. 439. 163-167 (1998)

Naomi Ihara、Reiko Akagi、Kohei Ejiri、Takafumi Kudo、Kazumichi Furuyama、Hiroyoshi Fujita：“大鼠胎盘血红素代谢酶基因表达的发育变化”FEBS Letters。

Ihara, N: "Developmental changes of heme metabolism in fetal period"J. Jpn. Soc. Study Women's Nutr. Metab. 3. 53-54 (1997)

Ihara，N：“胎儿期血红素代谢的发育变化”J。

伊原 直美: "ラット胎生期におけるヘム代謝の動態に関する研究" 日本産婦人科栄養・代謝研究会誌. 3・1. 63-64 (1997)

伊原直美：“大鼠胚胎期血红素代谢动态的研究”日本妇产科营养代谢研究会杂志3・1（1997）。

Masuyama H, Hiramatsu Y, Kudo T: "Effect of epidermal growth factor on placental amino acid transport and regulation of epidermal growth factor receptor expression of hepatocyte in rat"J Perinat Med. 24. 213-220 (1996)

Masuyama H，Hiramatsu Y，Kudo T：“表皮生长因子对胎盘氨基酸转运的影响以及对大鼠肝细胞表皮生长因子受体表达的调节”J Perinat Med。