不同培养体系对脐血造血干细胞粒细胞-巨噬细胞集落形成单位的影响

目的比较H4534与GF-H4434两种甲基纤维素培养基对脐血生成粒细胞-巨噬细胞集落形成单位（CFU-GM）的影响。方法从新鲜脐血标本中分离出造血干细胞,接种于H4534和GF—H4434培养基,于37℃、5％二氧化碳饱和湿度条件下培养14—16d。结果在样本中CD34＋细胞百分率和有核细胞总数检测结果相似的情况下,H4534与GF—H4434培养条件下CFU-GM集落数分别为（55．71±28．24）／105与（66．28±31．99）／105,两者比较差异有统计学意义（u=4．16,P〈0．05）。GF-H4434培养条件下还产生了红细胞爆裂型集落形成单位（64．89±34．95）／105和粒细胞-红细胞-巨噬细胞-单核细胞集落形成单位（2．53±2．08）／105。结论GF—H4434甲基纤维素培养基中脐血样本CFU-GM集落形成能力更强,更适合脐血质量鉴定。     

贫血治疗对改善慢性心力衰竭预后的价值

目的:探讨低剂量重组人促红细胞生成素(rhEPO)加铁剂治疗重症慢性充血性心力衰竭合并贫血的临床安全性以及对临床预后的影响。方法:入选慢性心力衰竭纽约心功能分级Ⅲ级以上、左心室射血分数(LVEF)<0.4且血红蛋白<100 g/L的患者共128例,随机分为贫血治疗组(n=66)和对照组(n=62)。随访12个月,记录2组无事件生存时间、主要终点事件(心衰恶化住院、心衰死亡)、次要终点事件(非心衰死亡、猝死、心肌梗死、不稳定性心绞痛、卒中、动脉栓塞、药物不良反应导致停药)。比较两组存活患者治疗前后的LVEF、左心室室壁应力(MWS)、左心室质量指数(LVMI)以及肿瘤坏死因子-α(TNF-α)、高敏C反应蛋白(hsCRP)和B型利钠肽(BNP)水平。结果:与对照组比较,治疗组无事件生存时间延长,但心衰死亡和心衰恶化住院率无显著性差异;非心衰心血管事件治疗组未增加。治疗组MWS和LVMI在治疗后显著降低,与对照组差异显著,而LVEF、BNP、TNF-α以及hsCRP水平两组无差异。结论:低剂量rhEPO加用铁剂治疗可安全用于重症充血性心力衰竭合并贫血患者,能延长生存时间和改善左心室功能,但不降低心衰病死率和心衰恶化入院率。     

促红细胞生成素对老年肺癌贫血的疗效及安全性评价

目的观察促红细胞生成素(EPO)对老年肺癌贫血的治疗效果并评价其治疗安全性。方法以2011年5月至2013年6月收治的肺癌合并贫血的36例老年患者为研究对象,按随机数字表格法分为两组。对照组18例患者给予蔗糖铁注射液,观察组在对照组基础上加用EPO,两组在对症处理与营养支持上相同,且均不放化疗,治疗6周后比较两组疗效。结果治疗后两组患者的红细胞数、血红蛋白数及血细胞比容值均较治疗前明显升高(P0.05);观察组治疗后上述3个指标均明显高于采用对照组[(4.27±0.38)×1012/L vs.(3.53±0.42)×1012/L,(115.12±5.47)g/L vs.(95.64±5.66)g/L,(36.54±4.38)%vs.(31.41±3.13)%,均P0.05];观察组的总有效率94.44%也明显高于对照组的77.78%(P0.05)。结论 EPO治疗老年肺癌贫血安全有效,建议在治疗过程中对患者进行血压监测。     

The role of correction of anaemia in patients with congestive heart failure: a short review

Many patients with Congestive Heart Failure (CHF) are anaemic. This anaemia is associated with more severe CHF and a higher incidence of mortality, hospitalisation and morbidity. The only way to prove that the anaemia is causing this worsening of CHF is to correct it. We review here some of the published papers about correction of anaemia. Many studies show a positive effect of Erythropoietin (EPO) or its' derivatives when administered in combination with oral or IV iron, with improvements in left and right ventricular systolic and diastolic function, dilation and hypertrophy and renal function. In addition, a reduction in hospitalisations, diuretic dose, pulmonary artery pressure, plasma volume, heart rate, serum Brain Natriuretic Peptide levels, the inflammatory marker Interleukin 6, soluble Fas ligand - a mediator of apoptosis, and improvements in New York Heart Association class, exercise capacity, oxygen utilization, caloric intake, Quality of Life and the activity of Endothelial Progenitor Cells, have been observed. Iron deficiency may also play an important role in this anaemia, since improvements in CHF have also been reported following treatment with IV iron alone. However, until the ongoing large placebo-controlled studies of the EPO derivative darbepoetin or IV iron are completed, we will not know whether these treatments really influence CHF outcome.     

Inadequate erythropoietin response to anemia: definition and clinical relevance

Summary The development of a specific and sensitive immunoassay for the measurement of serum erythropoietin (s-Epo) allows to improve our understanding of the model of in vivo regulation of erythropoiesis. In most anemias, circulating hemoglobin level determines Epo production which in turn stimulates erythropoietic activity. The disruption of the expected feedback mechanism of Epo production leads to an inadequately low s-Epo. The definition of inadequate Epo response to anemia relies on the documentation of a downregulated dependence of s-Epo on Hb with respect to the same dependence in patients with a physiologically regulated erythropoiesis. Literature reports a wide range of so called adequate s-Epo response to anemia and a number of criteria for judging on the adequateness of s-Epo at a certain degree of anemia. The O/P (observed/predicted) ratio allows categorization of each individual patient. The clinical syndromes in which an inadequate Epo response has been reported are numerous and the mechanisms of defective Epo production are different. A number of evidences clearly point to a relation between responsiveness to r-Hu-Epo and inadequate Epo response. This inequivocabily confirms the role inadequate Epo response plays in the pathogenesis of anemia.     

Potential cost savings of erythropoietin administration in end-stage renal disease

BACKGROUND: In a Department of Veterans Affairs randomized controlled trial, a lower dose of recombinant human erythropoietin (epoetin) was shown to attain target hematocrit levels when administered subcutaneously compared with intravenously. Since epoetin is expensive, optimizing the therapeutic effect of epoetin using a strategy that includes subcutaneous administration could lead to substantial cost savings. METHODS: We used an economic cost projection model to estimate potential savings to the Medicare End-Stage Renal Disease Program that could occur during a transition from intravenous to subcutaneous administration of epoetin among hemodialysis patients. Data included clinical results from the Department of Veterans Affairs randomized controlled trial, the 1998 Centers for Medicare and Medicaid Services' End-Stage Renal Disease Core Indicators Survey, and the 1997-1998 Medicare claims files. In sensitivity analyses, we varied the expected dose reductions (10% to 50%) and the proportion of patients (25% to 100%) who switched to subcutaneous administration. RESULTS: Medicare cost savings were estimated at $47 to $142 million annually as 25% to 75% of hemodialysis patients who received epoetin intravenously switched to subcutaneous administration while reducing the dose by 32%. A minimal reduction (10%) in epoetin dose would result in Medicare cost savings of an estimated $15 to $44 million annually. CONCLUSION: Administering epoetin subcutaneously would provide substantial cost savings to Medicare. For the transition to occur, consensus among stakeholders is needed, especially among patients whose treatment satisfaction and health-related quality of life would be most affected.     

EPO促进胚胎神经干细胞向神经元分化的形态学研究

目的：探讨促红细胞生成素（erythropoietin ,EPO）促进神经干细胞（neural stem cells ,NSCs）分化的形态学表现,为细胞移植治疗脑部疾病和脑损伤提供实验依据。方法取大鼠14 d胚胎脑皮质先增殖培养,后贴壁分化培养。适时镜下观察,免疫细胞化学染色,用nestin鉴定NSCs ,GFAP鉴定神经胶质细胞、MAP2鉴定神经元。选取第3代 NSCs ,向培养基中分别添加不同剂量的 EPO ,浓度分别为0．5u/ml ,5u/ml ,50u/ml ,500u/ml ,并设不添加EPO的对照组,MAP2免疫荧光共聚焦显微镜观察NSCs向神经元方向的分化。结果1）鼠胚脑皮质在无血清悬浮培养形成大量神经球,并可传代,球内细胞均表达 nestin。分化培养,可检测出MAP2或GFAP阳性细胞。2）EPO≥5u/ml各组分化培养,表达MAP2阳性细胞显著升高（P＜0．05）。结论大鼠胚胎脑皮质体外培养可获得NSCs ;适当浓度EPO可提高NSCs向神经元的分化。     

促红细胞生成素对新生儿缺氧性心肌损伤的影响

目的探讨促红细胞生成素（EPO）对新生儿缺氧性心肌损伤的治疗效果和保护作用,分析其对预后的影响及作用机制,为临床治疗提供依据。方法选择2010年5月-2013年5月宁波大学医学院附属医院缺氧性心肌损伤的新生儿42例,随机分为观察组和对照组,每组各21例,对照组进行常规治疗;观察组在常规治疗基础上应用EPO治疗。检测两组患儿治疗前后的肌酸激酶（CK）及同工酶（CK-MB）、肌钙蛋白Ⅰ、血红蛋白（Hb）、网织红细胞（Ret）,并进行心电图（ECG）检查。观察患儿呼吸急促消失、精神状态好转和ECG恢复时间等指标。结果治疗后两组患儿CK、CK-MB和肌钙蛋白Ⅰ水平均低于治疗前,差异均有统计学意义（P〈0.05）;治疗后观察组CK、CK-MB和肌钙蛋白Ⅰ分别为（198.26±69.04）U/L、（26.9±9.56）U/L、（0.16±0.38）μg/L,均低于对照组[（242.30±103.41）U/L、（37.40±12.30）U/L、（0.54±0.17）μg/L],差异均有统计学意义（P〈0.05）。治疗后观察组Hb和Ret%分别为（171.52±20.83）g/L和（3.55±0.65）,均高于对照组[（155.43±21.42）g/L、（2.51±0.63）],差异均有统计学意义（P〈0.05）。观察组ECG异常率为19.05%,低于对照组（47.62%）,差异有统计学意义（P〈0.05）;观察组呼吸急促消失、精神状态好转时间和ECG恢复时间分别为（1.28±0.14）、（2.56±0.21）、（5.32±0.40）d,均低于对照组[（2.86±0.32）、（4.05±0.41）、（7.38±0.74）d],差异均有统计学意义（P〈0.05）。结论 EPO对新生儿缺氧性心肌损伤的治疗效果较好,能够促进心功能恢复,改善症状或体征,减少症状改善时间,改善预后。     

促红细胞生成素对心肺复苏后大鼠神经功能及脑细胞凋亡的影响

目的 探讨促红细胞生成素（EPO）对心肺复苏后大鼠神经功能及脑细胞凋亡的影响.方法 将成年雄性SD大鼠随机分为对照组和EPO组,每组24只,采用窒息法制备心肺复苏模型,神经功能缺损评分（NDS）法评价复苏后12 h、24 h大鼠的神经功能,于复苏后0h、12 h、24 h用RT-PCR法检测大脑皮层组织凋亡诱导因子（AIF）、caspas-3 mRNA的水平.结果 EPO组心肺复苏后12 h、24h NDS评分分别为（70.50±4.04）分和（65.88±2.64）分,与对照组[12 h：（60.00±3.38）分;24h：（54.50±2.56）分]比较,差异有统计学意义（P＜0.01）;EPO组AIF基因mRNA表达水平在复苏后12h和24 h分别为（1.31±0.26）、（1.87±0.17）,与对照组[12h：（1.88±0.18）;24h：（2.71±0.24）]比较显著降低（均P＜0.01）;EPO组caspase-3基因的mRNA表达水平在复苏后12h和24 h分别为（1.49±0.15）、（1.56±0.10）,与对照组[12 h：（1.68±0.10）;24h：（1.84±0.16）]比较显著降低（均P＜0.01）;结论 EPO可降低AIF、caspase-3 mRNA的转录,减少脑缺血和再灌注损伤导致的皮层神经细胞凋亡,改善心肺复苏后大鼠的脑功能.