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

一、促红细胞生成素衍生物血管再生机制的基础研究(1)促红细胞生成素的作用机制：促红细胞生成素对肢体缺血的作用与骨髓移植的细胞疗法一样强。去唾液酸促红细胞生成素通过产生Bcl-xL和通过在骨骼肌中产生PLGF而诱导血管生成，从而诱导抗细胞凋亡的作用。(2)促红细胞生成素和去唾液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：造成大鼠心肌缺血模型28天后，立即用渗透泵持续静脉滴注促红细胞生成素或去唾液酸促红细胞生成素500IU/kg/d。两组患者心脏瘢痕面积均有缩小，但促红细胞生成素的疗效优于促红细胞生成素。前者检测到心肌细胞血管内皮生长因子、CD31、eNOS和Bclxl的表达增加，推测去唾液红细胞生成素…促红细胞生成素治疗急性心肌梗死的临床试验。(1)新泻大学8例，昭和大学20例，独居大学1例，小林医院4例。(2)促红细胞生成素的急性效应(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反应的病例。(3)促红细胞生成素的慢性效应：我们计划在注射后6个月获得每个患者的所有临床数据，包括心功能，并将在今年8月完成方案后调查最终结果。(4)血清海普西丁浓度：海普西丁在铁代谢中起中心作用。我们发现急性心肌梗死后海普西丁的浓度模式发生了有趣的变化，并准备提交这一结果。较少

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