Basic research and clinical trial regarding vessel regeneration and cardiac protection with a derivative of erythropoietin

1 .促红细胞生成素衍生物血管再生机制的基础研究(1)asialoerythropoietin的作用机制：asialoerythropoietin对肢体缺血的治疗效果与骨髓植入细胞疗法一样强。亚洲促红细胞生成素通过产生Bcl-xL诱导抗凋亡作用，并通过产生骨骼肌PLGF诱导血管生成。(2)促红细胞生成素和异氰酸促红细胞生成素在大鼠心肌缺血再灌注损伤模型中的作用：我们在造缺血模型28 d后立即用渗透泵连续静脉输注500 IU/kg/d促红细胞生成素或异氰酸促红细胞生成素。两组心脏瘢痕面积均有所减少，但异氰酸促红细胞生成素的效果优于促红细胞生成素。前者组心肌细胞VEGF、CD31、eNOS、Bcl-xL均升高，推测asialoerythropoitin…More具有较强的抗凋亡和血管生成作用。促红细胞生成素治疗急性心肌梗死的临床研究。(1)新泻大学8例，昭和大学20例，Dokkyo大学1例，Kobari医院4例。(2)促红细胞生成素的急性作用（1个月内）：治疗组在入院后24小时内静脉滴注促红细胞生成素30分钟。没有出现高血压或红细胞增多症等不良事件。(3)促红细胞生成素的慢性效应：我们计划在注射后6个月获得每位患者包括心功能在内的所有临床数据，并在今年8月方案完成后调查最终结果。(4)血清hepcidin浓度：hepcidin在铁代谢中起核心作用。我们发现急性心肌梗死后hepcidin浓度模式有一个有趣的变化，并准备提交这一结果。少

I. Basic research regarding the mechanism of vessel regeneration through use of a derivative of erythropoietin(1) The mechanism of asialoerythropoietin: The effects of limb ischemia with asialoerythropoietin are as strong as cell therapy with bone marrow implantation. Asialoerythropoietin induces an anti-apoptotic effect via the production of Bcl-xL as well as angiogenesis via production of PLGF in skeletal muscle. (2) The effect of erythropoietin and asialoerythropoietin in a reperfusion injury model of rat myocardial ischemia: We applied continuous intravenous infusion of 500 IU/kg/day of erythropoietin or asialoerythropoietin using an osmotic pump immediately after making this ischemic model for 28 days. A decrease of the scar area in the heart was found in both groups, but the effect of asialoerythropoietin was superior to that of erythropoietin. In the former group, an increase of VEGF, CD31, eNOS, and Bcl-xL of myocyte was determined, and it was supposed that asialoerythropoietin … More has strong anti-apoptotic and angiogenic effects.II. Clinical trial of erythropoietin therapy for acute myocardial infarction.(1) Eight cases in Niigata University, 20 in Showa University, one in Dokkyo University, and 4 cases in the Kobari Hospital were registered in this study. (2) Acute effect of erythropoietin (within one month): We administered an intravenous drip infusion of erythropoietin for 30 minutes within 24hours after admission to the hospital in the treatment group. There were no cases indicating adverse events such as hypertension or polycythemia. (3) Chronic effect of erythropoietin: We plan to get all clinical data of each patient including cardiac function 6 months after injection, and will investigate the final results after completion of the protocol in August this year. (4) Serum hepcidin concentration: Hepcidin plays a central role in iron metabolism. We found an interesting change in the pattern of the hepcidin concentration after acute myocardial infarction and are preparing to submit this result. Less