Roles of prostanoids in cardiovascularsystem revealed from studies using knockout mice

使用基因敲除小鼠的研究揭示了前列腺素在心血管系统中的作用

• 批准号: 11470020
• 负责人: USHIKUBI Fumitaka
• 金额: $ 9.34万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470020/
• 关键词: prostanoids; prostaglandin; thromboxane; knockout mice; prostanoid receptor; cardiovascular system; platelets; ischemia-reperfusion; 循環器; 心筋虚血; 心肥大

The prostanoids are lipid mediators showing variable effects on many organs in the body including the cardiovascular system. Their roles in the system, however, have been largely unknown. We attempted to clarify these roles using mice lacking the prostanoids receptors individually. We first established variable methods for the analysis. These include in vivo models such as for cardiac hypertrophy, thromboembolism, vascular remodeling and renovascular hypertension, and in vitro systems for culture of vascular smooth muscle cells, cultures of cardiomyocytes from fetal or adult mice, platelet aggregation and vascular tone. We next examined the roles of the prostanoids using the established methods and knockout mice, Prostaglandin (PG)l_2 was found to be a potent mediator to protect the cardiomyocytes from ischemia-reperfusion injury. PGE_2 potentiated the platelet activation induced by other platelet stimulants, such as thromboxane A_2 and ADP. Furthermore, this potentiating effect on the platelets was verified to be important in both hemostasis and thromboembolism. Other roles of the prostanoids in the cardiovascular system would be clarified in near future, because several interesting results have been already obtained in the present project. They include the roles in various pathological conditions such as cardiac hypertrophy, vascular remodeling and renovascular hypertension

前列腺素是一种脂质介质，对包括心血管系统在内的许多器官都有不同的影响。然而，他们在这个体系中的作用在很大程度上是未知的。我们试图用单独缺乏前列腺素受体的小鼠来阐明这些作用。我们首先建立了变量分析方法。这些包括心脏肥大、血栓栓塞、血管重塑和肾血管性高血压的体内模型，以及血管平滑肌细胞培养、胎儿或成年小鼠心肌细胞培养、血小板聚集和血管张力的体外系统。结果表明，前列腺素（PG）l_2对心肌细胞缺血再灌注损伤具有保护作用。PGE_2可增强其他血小板刺激剂（如血栓素A_2和ADP）诱导的血小板活化。此外，这种对血小板的增强作用被证实在止血和血栓栓塞中都是重要的。前列腺素在心血管系统中的其他作用将在不久的将来得到澄清，因为在本项目中已经获得了几个有趣的结果。它们包括在各种病理条件下的作用，如心脏肥大、血管重塑和肾血管性高血压

项目成果

Xiao, C.-Y. et al.: "Roles of prostaglandin I_2 and thromboxane A_2 in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors"Circulation. 104. 2210-2215 (2001)

肖，C.-Y。

Narumiya, S.: "Prostanoid receptors: structures, properties and functions"Physiol. Rev.. 79. 1193-1226 (1999)

Narumiya, S.：“前列腺素受体：结构、特性和功能”Physiol。

Watanabe,K. et al.: "Role of the prostaglandin E receptor subtype EP_1 in colon carcinogenesis."Cancer Res.. 59. 5093-5096 (1999)

渡边，K.

Matsuoka, T.: "Prostaglandin D_2 as a mediator of allergic asthma"Science. 287. 2013-2017 (2000)

Matsuoka, T.：“前列腺素 D_2 作为过敏性哮喘的介质”科学。

Okada, Y.: "Characterization of prostanoid receptoi~s mediating contraction of the gastric fundus and ileum : Studies using mice deficient in prostanoid receptors"Br. J. Pharmacol. 131. 745-755 (2000)

Okada, Y.：“介导胃底和回肠收缩的前列腺素受体的表征：使用缺乏前列腺素受体的小鼠进行的研究”Br。