权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The studies on the role of prostacyckin in inflammation and on its mechanism of action.

前列环素在炎症中的作用及其作用机制的研究。

基本信息

批准号：
18592060
负责人：
YOKOYAMA Chieko
金额：
$ 2.53万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592060/
关键词：
prostaglandih prostacyclin kidney inflammation vascular disorders bone

项目摘要

Prostacyclin (PGI_2) is the powerful physiological lipid mediator which has the platelet anti-aggregating and vasorelaxant effects, and regulation of the cell growth. Arachidonic acid is converted to PGH_2 by cyclooxygenase and PGI_2 is converted from the PGH_2 by the catalytic reaction of PGI_2 synthase (PGIS). PGI_2 acts through the PGI_2 receptor on the cell membranes and also acts as the endogenous ligand of PPARδ which is the nuclear receptor. Recently, relationship of inflammation and PGI2-PPARδ signaling has gotten attention. However, the detail mechanism is not clear. In this study, we have tried to clarify the effects of PGI_2 on inflammation and the reaction mechanisms. The obtained results are as follows.1. Administration of PGI_2 receptor agonist, Beraprost sodium was not prevented development of kidney disorders of PGI_2-deficient mice (PGIS-KO mice). The blood urinary nitrogen (BUN) levels of the PGIS-Kotg mice, which were generated by breeding PGIS-KO mice and PGIS transgenic mice, significantly decreased compared with those of PGIS-KO mice. The result suggests that endogenous PGI_2 may regulate the progression of kidney diseases of PGI2-deficient mice and may have some anti-inflammatory effect.2. Little is known about the relation between PGI_2 and the bone metabolism. To study on the relationship we have observed influence of the PGI_2 deficiency in bone formation. As a result, we have recognized the increase of trabecular bone density and the decrease of total bone density in the fibulae of female PGI_2-deficient mice. The results suggest that PGI2 may participate in the maintenance of the quantity of the normal bone and of microstructure of the bone.

前列环素(PGI_2)是一种强大的生理性脂质介质，具有抗血小板聚集、舒血管、调节细胞生长的作用。花生四烯酸在环氧合酶的作用下转化为PGH_2，在PGI_2合成酶(PGIS)的催化作用下从PGH_2转化为PGI_2。PGI2通过细胞膜上的PGI2受体发挥作用，同时也是核受体PPARδ的内源性配体。近年来，炎症与前列腺素I2-PPARδ信号转导通路的关系受到关注。然而，具体机制尚不清楚。本研究试图阐明前列腺素I_2的抗炎作用及其作用机制。得到的结果如下：1.研究结果。给予PGI2受体激动剂贝拉前列素钠不能阻止PGI2基因缺陷小鼠(PGIS-KO小鼠)肾脏疾病的发生。与pGIS-KO小鼠相比，pGIS-Kotg小鼠和pGIS转基因小鼠产生的血尿氮(BUN)水平显著降低。提示内源性PGI_2可能对PGI_2缺陷小鼠肾脏疾病的进展有一定的调节作用，并可能具有一定的抗炎作用。前列环素与骨代谢的关系目前还知之甚少。为了研究两者之间的关系，我们观察了PGI_2缺乏对骨形成的影响。因此，我们认识到雌性PGI_2缺陷小鼠的腓骨骨小梁密度增加，总骨密度降低。结果提示，PGI2可能参与了正常骨量的维持和骨微结构的维持。