Serum erythropoietin level: Relationships to blood hemoglobin concentration and erythrocytic activity of the bone marrow

Summary The question as to whether the serum concentration of erythropoietin is relatively high for the degree of anemia in patients with erythrocytic hypoplasia has regained interest, since recombinant human-like erythropoietin has become available as a drug for replacement therapy. We have compared the concentration of serum immunoreactive erythropoietin in nonrenal anemic patients with erythrocytic hypoplasia (22 cases) or active erythropoiesis (82 cases). In both groups a negative correlation was determined between the blood hemoglobin concentration and the logarithm of the erythropoietin concentration. However, the two regression lines were not identical, and the serum erythropoietin concentration was significantly higher for the degree of anemia in the patients with erythrocytic hypoplasia. Additional measurements in four patients suffering from acute leukemia with marrow failure showed that the erythropoietin concentration decreased towards the values observed in anemic patients with active erythropoiesis when the erythron recovered in the early phase of complete remission. These data support the idea that, independent of the O₂ offer, the proliferating erythrocytic progenitors by negative feedback lower the blood level of erythropoietin.Abbreviations Epo Erythropoietin - AML acute myelogenous leukemia - CML chronic myelogenous leukemia - ALL acute lymphoblastic leukemia - CLL chronic lymphatic leukemia - PBS phosphate buffered saline - BSA bovine serum albumin - Hb hemoglobin - DNA desoxyribonucleic acid A preliminary report of these studies was given at the XIIth International Symposium on Structure and Function of Erythroid Cells in Berlin, August 1989 [18]     

Haematological improvement by long-term administration of recombinant human granulocyte-colony stimulating factor and recombinant human erythropoietin in a patient with severe aplastic anaemia

A 6-year-old girl with post-hepatitic severe aplastic anaemia was referred to our hospital. Haematological examination showed a haemoglobin level of 5.2 g/dl, platelet count of 8,000/l, and white blood cell count of 130/l with 17% neutrophils. She was treated with recombinant human granulocytecolony stimulating factor (15 g/kg/day i.v.) and cyclosporin A (6 mg/kg/day p.o.). The absolute neutrophil count gradually increased, but Hb and platelets were not improved. The intravenous administration of recombinant human erythropoietin (100 U/kg three times a week) was started, and the reticulocyte count reached 20000/l on day 12. The platelets increased to 81000/l after 16 months of combined administration of recombinant human granulocyte-colony stimulating factor, recombinant human erythropoietin and cyclosporin A. After 20 months of combined administration, the haematological results were: Hb, 13.1 g/dl; platelets 80000/l: WBC, 9500/l with 40% neutrophils. After recombinant human granulocyte-colony stimulating factor treatment, the myeloid elements of the bone marrow and the number of granulocyte-macrophage colony forming units increased. Bone marrow erythropoiesis and erythroid colonies also increased after recombinant human erythropoietin administration. The clinical course suggested a beneficial effect of haemopoietic growth factors and cyclosporin A in post-hepatitic aplastic anaemia.     

国产重组人类促红细胞生成素预防早产儿贫血

目的　观察重组人类促红细胞生成素 (r Hu EPO,商品名宁红欣 )对早产儿贫血的预防作用。　方法　将来自四所医院的 5 1例胎龄小于 35周、体重小于 2 0 0 0 g的早产儿随机分为预防组(31例 )和对照组 (2 0例 )。预防组予 r Hu EPO2 5 0 IU/ (kg·次 ) ,静脉或皮下注射 ,隔日 1次 ,每周 3次 ,共 4周。观察两组早产儿血红蛋白 (Hb)、红细胞压积 (Hct)、网织红细胞 (Ret)、血清铁及促红细胞生成素 (EPO)的动态变化。　结果　两组早产儿生后 Hb、Hct均逐渐下降 ,但预防组下降明显小于对照组 ,经 t检验 ,两组之间差异有显著性 (P<0 .0 0 1)。对照组有 4例输血 ,而预防组无一例输血 ,经精确 χ2检验 ,差异有显著性 (P=0 .0 19)。预防组 1周末 Ret较对照组明显升高 ,差异有显著性 (P<0 .0 5 )。预防组 2周末血清铁低于对照组 ,4周末更甚 ,经比较差异有非常显著性 (P<0 .0 1)。预防组EPO水平较对照组明显上升 ,差异有非常显著性 (P<0 .0 1)。　结论　早产儿预防性应用 r Hu EPO可减轻 Hb、Hct、Ret的下降程度 ,不需要输血和输血次数减少 ,r Hu EPO预防早产儿贫血有一定效果。     

大剂量促红细胞生成素治疗肾性贫血的疗效观察

目的:观察大剂量促红细胞生成素治疗肾性贫血的疗效和安全性。方法:将60例肾性贫血患者随机分为治疗组和对照组。治疗组给予促红细胞生成素9000IU皮下注射,1次/wk;对照组给予促红细胞生成素3000IU皮下注射,3次/wk,均连用6wk。结果:治疗组和对照组的有效率分别为93.3%、90.0%(P>0.05),但前者较后者每周注射次数减少,费用低,且不良反应无明显增加。结论:大剂量促红细胞生成素治疗肾性贫血疗效确切、安全、可靠。     

促红细胞生成素在子宫内膜异位症组织的表达

目的探讨促红细胞生成素(Epo)在子宫内膜异位症(EMs)发生中的病理生理作用及其临床意义。方法应用免疫组织化学SABC法、mRNA原位杂交法检测39例子宫内膜异位症的异位内膜及35例正常子宫内膜Epo的组织定位和表达强度,并对比其差异。结果Epo、EpomRNA的表达主要定位于腺体细胞胞质、胞核,间质细胞表达不明显。异位内膜组织Epo、EpomRNA表达分别为9.68±2.90,3.08±0.48,明显高于正常对照的4.54±2.86,0.55±0.46,差异有高度显著性(P<0.01);Epo、EpoRNA在EMs组、正常对照组的增殖期和分泌期表达相比,差异均无显著性(P>0.05);EMs组EpomRNA与AFS分期呈正相关(r=0.979,P=0.013)。结论Epo通过旁分泌或自分泌方式过度转录表达引起的局部新生血管生成增强可能是子宫内膜异位症发生的机制之一。     

长期静脉补铁改善血液透析患者肾性贫血的作用

目的探讨血液透析患者长期静脉补铁改善肾性贫血的效果以及对促红细胞生成素(EPO)作用的影响。方法选择56例病情稳定的血液透析患者随机分成两组:静脉组和口服组,各28例,疗程6个月。静脉组:于每次透析时补给100mg右旋糖酐铁,共10次,然后每2周给予维持量100mg。口服组:前3个月口服硫酸亚铁525mg/d,后3个月停服,按上述方法改用静脉补铁。比较两组贫血治疗效果、铁代谢和生化指标的变化、EPO用量以及不良反应发生情况。结果治疗后静脉组血红蛋白(Hb)、红细胞压积(Hct)、血清铁蛋白(SF)、转铁蛋白饱合度(TSAT)进行性升高,3个月后80%以上的患者贫血得到纠正,EPO用量较基数减少约28%。口服组治疗3个月时,Hb和Hct增幅不大,而SF和TSAT则逐月降低;第4个月起改用静脉补铁后,SF、TSAT很快升高,贫血迅速得到改善,EPO用量开始明显减少。结论长期静脉补铁不仅能及时有效地改善血液透析患者的贫血,减少EPO用量,而且经济、安全。     

肿瘤坏死因子 α、白介素 6和红细胞生成素与小儿慢性病贫血的相关性分析

目的探讨小儿慢性病贫血(ACD)时外周血肿瘤坏死因子(TNF) α、白介素(IL) 6与红细胞生成素(EPO)的变化及其在发病机制中的作用。 方法2002年4月至2004年12月常州市儿童医院收治ACD患儿19例(ACD组)，采用放射免疫分析方法测定患儿外周血清中TNF α、IL 6、EPO水平；对照组为17例上呼吸道感染恢复期患儿。 结果与对照组比较，ACD组患儿血清中TNF α、IL 6均显著增高(P<0.05)。血清TNF α、IL 6与血清铁蛋白质量浓度呈正相关。 结论免疫及炎症反应所产生的细胞因子TNF α、IL 6可能通过干扰铁代谢和抑制EPO生成、钝化对EPO的反应等途径介导了ACD的发生和发展过程。     

大鼠视神经挫伤后生长相关蛋白的变化及重组人促红细胞生成素的作用

目的 研究大鼠视神经挫伤后视神经生长相关蛋白( GAP-43)的变化及重组人促红细胞生成素(rhEPO)的作用.方法 建立外伤性视神经损伤的动物模型,随机分为正常对照组、损伤组(视神经钳夹+生理盐水)及rhEPO组(视神经钳夹+rhEPO),于损伤后1d、4d、7d、14 d和28 d对各组视网膜及视神经进行形态学观察,免疫组化染色法测定视神经GAP-43的活性.结果 rhEPO组较损伤组视网膜及视神经病变明显减轻；在损伤后4d和7d趼组间损伤远端GAP-43表达差异无统计学意义(P＞0.05)；14 d和28 d rhEPO组损伤远端GAP-43表达较损伤组明显升高(P＜0.05).结论 rhEPO对视神经不完全损伤可促进视网膜神经节细胞存活与视神经纤维再生修复.     

红细胞生成素对慢性肾衰竭大鼠残肾组织归巢因子表达的影响

目的 观察红细胞生成素(EPO)对慢性肾衰竭(CRF)大鼠肾组织归巢因子表达的影响.方法 采用分阶段5/6肾切除制备大鼠CRF模型.实验动物随机分为3组:假手术组、CRF模型组和EPO治疗组.从第3周开始,治疗组大鼠每次皮下注射重组人EPO 50 IU/kg,每周3次,共6周.8周后检测各组大鼠血肌酐(Scr)、血尿素氮(BUN)、尿蛋白、血红蛋白(Hb)；采用实时荧光定量PCR、Western印迹和免疫组化方法检测残肾组织EPO及其受体(EPOR)、归巢因子及其受体(SDF-1、CXCR4、Ang-1、Tie2、SCF、c-Kit)的表达.结果 与模型组比较,EPO治疗可上调残肾组织归巢因子及其受体(SDF-1、CXCR4、Ang-1、Tie2、SCF、c-Kit)mRNA和蛋白的表达(均P＜0.05)；同时,EPO治疗还可上调残肾组织EPO及EPOR的mRNA和蛋白的表达(均P＜ 0.05).此外,EPO治疗还能下调大鼠Scr、BUN和尿蛋白水平(均P＜0.05),上调Hb水平(P＜0.05).结论 EPO能改善慢性肾衰竭大鼠的肾功能,这种作用可能与其激活残肾组织归巢因子而参与损伤肾脏的修复有关.     

Comparison of Neurite Outgrowth Induced by Erythropoietin (EPO) and Carbamylated Erythropoietin (CEPO) in Hippocampal Neural Progenitor Cells

A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubule-associated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.