First Department of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Prostaglandins Other Lipid Mediat. 2009 Dec;90(3-4):85-8. doi: 10.1016/j.prostaglandins.2009.09.002. Epub 2009 Sep 16.
We investigated whether systemically administered EP2 receptor agonists would stimulate angiogenesis in the emphysematous lungs of mice. Saline or porcine pancreatic elastase was intratracheally administered to C57BL/6J mice to induce the formation of emphysematous lesions, and 4 weeks later the mice were intraperitoneally injected with an EP2 receptor agonist, ONO-AE1-259 or PGE2, or saline on days 1-5 each week for 3 weeks. Intraperitoneal ONO-AE1-259 in the mice in the intratracheal saline group increased pulmonary capillary volume to 114.9% of the control value (P<0.05), and when administered to the intratracheal elastase group, ONO-AE1-259 partially restored pulmonary capillary volume, from 70.9% of the control value to 88.3% of the control value (P<0.05). Intraperitoneal PGE2 tended to increase pulmonary capillary volume in the mice in the intratracheal saline group (P=0.07) but not in the intratracheal elastase group. Intraperitoneal ONO-AE1-259 and PGE2 each increased the concentration of vascular endothelial growth factor (VEGF) and the number of endothelial progenitor cells (EPCs) in circulating blood. These results suggest that systemically administered ONO-AE1-259 stimulates pulmonary angiogenesis in an elastase-induced murine model of emphysema.
我们研究了系统给予 EP2 受体激动剂是否会刺激肺气肿小鼠肺部的血管生成。通过气管内给予生理盐水或猪胰弹性蛋白酶来诱导 C57BL/6J 小鼠肺气肿病变的形成，4 周后，每周 1-5 天通过腹腔内注射 EP2 受体激动剂 ONO-AE1-259 或 PGE2 或生理盐水，共 3 周。在气管内生理盐水组的小鼠中，腹腔内给予 ONO-AE1-259 将肺毛细血管容积增加至对照值的 114.9%（P<0.05），当给予气管内弹性蛋白酶组时，ONO-AE1-259 部分恢复了肺毛细血管容积，从对照值的 70.9%增加到对照值的 88.3%（P<0.05）。腹腔内 PGE2 倾向于增加气管内生理盐水组小鼠的肺毛细血管容积（P=0.07），但对气管内弹性蛋白酶组无影响。腹腔内 ONO-AE1-259 和 PGE2 均增加了循环血液中血管内皮生长因子 (VEGF)的浓度和内皮祖细胞 (EPC)的数量。这些结果表明，系统给予 ONO-AE1-259 刺激了弹性蛋白酶诱导的肺气肿小鼠模型中的肺血管生成。
