Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
J Korean Med Sci. 2012 Sep;27(9):1073-8. doi: 10.3346/jkms.2012.27.9.1073. Epub 2012 Aug 22.
This study was conducted to investigate the effects of erythropoietin (Epo) on both acute and chronic limb ischemia (ALI and CLI) and to evaluate the differences in mechanisms according to the method of Epo administration. Hindlimb ischemia was made in BALB/c mice with femoral artery ligation. The mice were divided into four groups: Group 1 (control, no treatment), Group 2 (ALI, early multiple doses), Group 3 (ALI, early single high dose), Group 4 (CLI, late multiple doses). Blood flow ratio significantly increased in Group 2 in 4 weeks. Expression of pAkt and Erythropoietin receptor were significantly higher in Group 2 on postoperative day (POD) 7. The number of CD31- and vascular endothelial growth factor-positive cells were significantly higher in Group 2 on POD 7 and 56. Group 3 and 4 showed a tendency of higher cell counts than the control. The early sustained Epo was effective in improving blood flow through angiogenesis. In chronic phase, weekly multiple dosing of Epo induced angiogenesis, however, the blood flow ratio did not increase significantly. The results of this study suggest that Epo administration during the acute phase followed by maintenance for several days may be important for increasing blood flow and angiogenesis.
本研究旨在探讨促红细胞生成素（Epo）对急性和慢性肢体缺血（ALI 和 CLI）的影响，并根据 Epo 给药方式评估其机制差异。通过股动脉结扎法在 BALB/c 小鼠中诱导后肢缺血。将小鼠分为四组：第 1 组（对照组，未治疗）、第 2 组（ALI，早期多次剂量）、第 3 组（ALI，早期单次高剂量）、第 4 组（CLI，晚期多次剂量）。在第 4 周，第 2 组的血流比显著增加。第 2 组在术后第 7 天（POD）时 pAkt 和促红细胞生成素受体的表达显著升高。第 2 组在 POD7 和 56 时 CD31-和血管内皮生长因子阳性细胞的数量显著增加。第 3 组和第 4 组的细胞计数高于对照组的趋势。早期持续给予 Epo 通过血管生成改善血流是有效的。在慢性期，Epo 每周多次给药诱导血管生成，但血流比没有显著增加。本研究结果表明，在急性阶段给予 Epo 并维持数天可能对增加血流和血管生成很重要。
