胎児の生体防御機構としての羊水, 卵膜の役割とその破綻

金山, 尚裕

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胎児の生体防御機構としての羊水, 卵膜の役割とその破綻

http://hdl.handle.net/10271/118

名前 / ファイル	ライセンス	アクション
110002109082.pdf (1.4 MB)

Item type

学術雑誌論文 / Journal Article(1)

公開日

2013-08-27

タイトル

胎児の生体防御機構としての羊水, 卵膜の役割とその破綻

言語

タイトル

Intrauterine Defensive Mechanism of Amniotic Fluid and Fetal Membranes

言語

jpn

資源タイプ

資源タイプ識別子

http://purl.org/coar/resource_type/c_6501

資源タイプ

journal article

アクセス権

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

その他のタイトル

【シンポジウム：子宮内環境と胎児】

著者

金山, 尚裕

書誌情報

ja : 日本産科婦人科學會雜誌
en : Acta Obstetrica et Gynaecologica Japonica

巻 46, 号 8, p. 673-685, 発行日 1994-08-01

出版者

日本産科婦人科学会

言語

権利

権利情報

権利

権利情報

本文データは学協会の許諾に基づきCiNiiから複製したものである

抄録

内容記述タイプ

Abstract

内容記述

To determine the intrauterine defensive role of urinary trypsin inhibitor (UTI), we studied the effects of UTI in amniotic fluid, fetal membranes and myometrium. The level of UTI was 94±34U/ml in neonatal urine (compared to adult urine 8.0±6.0U/ml) and 88±37U/ml in amniotic fluid. This may indicate that the main source of UTI in the amniotic fluid is the fetal urine.
UTI was found to be concentrated in vernix, fetal intestine, amniotic membranes and uterine myometrium. Immunostaining of term amnion revealed a dark staining for UTI, whereas in premature deliveries UTI staining was markedly decreased. In myometrium, the concentration of UTI was found to be increased during pregnancy compared to non pregnant myometrium. Also, placentas were well stained for UTI in term pregnancy. Thus UTI has an important role in amniotic fluid, fetal membranes, placenta and uterine muscles.
UTI has an inhibitory effect on several enzymes and cytokines. UTI was found to inhibit neutrophil elastase activity as well as trypsin activity. Its inhibitory activity was increased in the presence of lipid. LPS stimulated amnion cells trapped more UTI than unstimulated amnion cells. UTI in amnion cells was released after addition of 1% meconium solution. UTI was also found to inhibit the effect of IL-1, TNF and interleukin-8 on amnion. These results indicate that UTI localized in amnion is important in the protection of fetal membrane especially against bacterial infections and cytokines.
It is known that endothelin (ET), prostaglandin F_<2α> (PGF_<2α>) and oxytocin can induce uterine contraction. UTI could inhibit uterine contractions stimulated by ET, PGF_<2α> and oxytocin in isometric contraction test. UTI could also inhibit cervical maturation induced by interleukin-8. Therefore UTI is essential for maintenance of pregnancy.
From the isometric contraction tests, we assumed that UTI might works through regulation of calcium entry or availability in the cells. Initial increase in intracellular calcium was also inhibited by UTI pre incubation dose dependantly. We examined the change in intracellular calcium at single cell level by digital image analysis with Fura 2AM as a calcium probe. At resting level UTI incubation did not produce any significant changes in intracellular free calcium. Thrombin, LPS, interleukin-8 and ET-1, known calcium agonists could increase intracellular calcium in fibroblasts, amnion and uterine myocytes. Whereas as the same doses of those known calcium agonists could not change the intracellular free Ca^<2+> concentrations in UTI pre incubated fibroblasts, amnion cells and uterine smooth muscle cells. Pre incubation with 2nM EGTA could inhibit the initial rise in intracellular calcium that reflects the calcium release from intracellular stores. However pre incubation with UTI, the initial rise in intracellular calcium was also inhibited. These results agreed the result of inhibition of myometrial contraction by UTI pre incubation in isometric contraction tests. The inhibitory effect of UTI on calcium mobilization and entry was suggested by this study. Increased intracellular free calcium also functions as a second messenger that determines the cellular synthetic activities in many cells. With the idea that UTI inhibits the synthetic activities in cells, we examined the effect of UTI pre incubation on production of interleukin-8, collagenase and prostaglandin from the amniotic cells and fibroblasts. LPS stimulated amnion cells and the fibroblast cultures and significantly increased production of interleukin-8, colIagenase and prostaglandin from them. Whereas as pre incubation with UTI, the production of interleukin-8, collagenase and prostaglandin from the amnion cells and fibroblasts was depressed. LPS could increase significantly the appearance of mRNA of interleukin-8 in amnion and fibroblast cells. We also examined the effect of UTI pre incubation on the appearance of mRNA in LPS stimulated cells. The appearance of mRNA of interleukin-8 in those cells was inhibited in the presence of UTI. From these series of experiments, we concluded that UTI regulates the production of inflammatory mediators by the control of intracellular free Ca^<2+> : a second messenger.
We treated mild cases of imminent preterm delivery with UTI suppository or ritodrine infusions. The treatment with UTI suppository could significantly prolong the pregnancy than that with ritodrine. The preterm birth rate was also significantly lower in UTI treated cases than in ritodrine treated cases. Therefore, treatment with UTI vaginal suppository would be a new and very useful for imminent preterm delivery.

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0300-9165

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胎児の生体防御機構としての羊水, 卵膜の役割とその破綻

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