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

前列环素（PGI_2）是一种有效的生理性脂质介质，具有抗血小板聚集、血管舒张和调节细胞生长的作用。花生四烯酸通过环加氧酶转化为PGH_2， PGI_2合成酶（PGIS）催化将PGH_2转化为PGI_2。PGI_2通过细胞膜上的PGI_2受体起作用，并作为核受体PPARδ的内源性配体。近年来，炎症与PGI2-PPARδ信号的关系引起了人们的关注。然而，具体机制尚不清楚。在本研究中，我们试图阐明PGI_2对炎症的作用及其反应机制。得到的结果如下：1。PGI_2受体激动剂Beraprost钠不能阻止PGI_2缺陷小鼠（PGI_2- ko小鼠）肾脏疾病的发生。通过培育PGIS- ko小鼠和转基因PGIS小鼠产生的PGIS- kotg小鼠的血尿氮（BUN）水平与PGIS- ko小鼠相比显著降低。提示内源性PGI_2可调节pgi2缺陷小鼠肾脏疾病的进展，并可能具有一定的抗炎作用。PGI_2与骨代谢的关系尚不清楚。为了研究二者之间的关系，我们观察了PGI_2缺乏对骨形成的影响。因此，我们发现雌性pgi_2缺失小鼠的骨小梁骨密度增加，腓骨总骨密度降低。提示PGI2可能参与正常骨的数量维持和骨的微结构维持。

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.