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Investigation of the roles of arachidonic acid metabolite at the process of placenta discharge at delivery of cattle and development of new delivery induction method

花生四烯酸代谢物在牛分娩时胎盘排出过程中的作用研究及新分娩诱导方法的开发

基本信息

批准号：
16380182
负责人：
KAMADA Hachiro
金额：
$ 10.47万
依托单位：
National Agricultural Research Organization
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

As a time of delivery can not be correctly expected, the attendance in the midnight delivery is unavoidable and hard labor for stock raising farmers. The delivery-control technique to alleviate mental and physical strain on the manager are required. The fetal delivery serving as the first stage of delivery is well understood; however, researches are not in progress regarding the release of unneeded placenta serving as the second stage, and the mechanism which induces the placental release has not been known yet. In this study, identification of signal for placenta release and its practical application for delivery induction method were investigated. It is known that a kind of matrix metalloproteinases (MMP) likely relates to placenta release. So we tried to search for the activator of placental MMP using cultured bovine fibroblast derived from placenta. First, we forcused on the metabolites of arachidonic acid (Ara) because those play important roles at the process of delivery. Cyclooxygenase metabolites of Ara (prostanoid) had no activity on MMP activation; however, one of lipoxygenase metabolites showed a strong activity on MMP activation. Delivery induction using prostaglandin (PG) frequently results in retained placenta. However, we succeeded in placenta release of those cows by injection of lipoxygenase metabolite of Ara. And the zymographic pattern of MMP activity of placenta in this case was same as that in normal delivery. While a large amount of proMMP (inactive form) accumulation in placenta was observed in the cases of PG-induced delivery and naturally occoured retained placenta, which suggested the failure of MMP activation. These results indicated that lipoxygenase metabolite of Ara is a signal for MMP activation and placenta release at a delivery. We could develope a new method of delivery induction without retained placenta.

由于交割时间不能准确预期，午夜交割的到场是养殖户不可避免的繁重劳动。需要使用交付控制技术来减轻经理的精神和身体压力。胎儿分娩作为分娩的第一阶段已为人们所熟知，但作为第二阶段的多余胎盘的释放尚无研究进展，导致胎盘释放的机制尚不清楚。本研究对胎盘释放信号的识别及其在引产方法中的实际应用进行了研究。已知一种基质金属蛋白酶(MMPs)可能与胎盘释放有关。因此，我们试图利用体外培养的牛胎盘成纤维细胞来寻找胎盘基质金属蛋白酶的激活剂。首先，我们强制使用花生四烯酸(Ara)的代谢物，因为它们在递送过程中起着重要作用。阿糖胞苷(前列腺素)的环氧合酶代谢产物对基质金属蛋白酶无激活作用，而其中一种脂氧合酶代谢产物具有较强的激活基质金属蛋白酶活性。使用前列腺素(PG)诱导分娩通常会导致胎盘滞留。然而，我们通过注射Ara的脂氧合酶代谢产物成功地释放了这些奶牛的胎盘。胎盘基质金属蛋白酶活性的酶谱与正常分娩时相同。而在PG引产和胎盘自然滞留的胎盘中，观察到大量的非活性形式的前MMPs积聚，提示MMPs激活失败。这些结果表明，Ara的脂氧合酶代谢产物是一种在分娩时激活基质金属蛋白酶和释放胎盘的信号。我们可以开发一种新的无胎盘滞留的引产方法。