促红细胞生成素对神经系统的保护

促红细胞生成素作为一种传统意义上的造血生长因子,有着造血作用以外的重要生物学作用。促红细胞生成素可受缺氧诱导,在神经系统广泛表达;其对神经系统的保护是通过对神经元、神经胶质、神经祖细胞以及脑血管内皮细胞功能的影响而实现的。促红细胞生成素强大神经保护潜力的发现,开辟了神经系统疾病新的治疗途径。     

促红细胞生成素对缺氧缺血新生鼠脑损伤学习记忆能力的影响

目的研究促红细胞生成素(EPO)对缺氧缺血性脑损伤(HIBD)新生大鼠海马的近期病理改变和远期学习记忆功能的影响。方法新生7d大鼠随机分3组:假手术组、HIBD模型组和HIBD EPO组。HIBD术后72h观察脑组织病理改变、海马CA1区凋亡抑制蛋白Bcl-2的表达,术后28d评估海马学习记忆功能。结果EPO治疗能显著减轻缺氧缺血侧大脑半球水肿、梗死和出血等病理学改变。免疫组化结果显示HIBD后72h缺血侧海马CA1区Bcl-2蛋白表达量均为HIBD EPO组>HIBD组>假手术组,3者间比较差异有统计学意义。Morris水迷宫定位航行实验结果显示,5d总平均逃逸潜伏期HIBD组(67.93±7.29)s,HIBD EPO组(42.95±7.29)s,假手术组(29.67±6.95)s,平均逃逸潜伏期在不同时段和不同实验组之间的差异有统计学意义;空间探索实验示:HIBD组站台周边区域I搜索时间和搜索路程与HIBD EPO组、假手术组间差异均有统计学意义,而HIBD EPO组和假手术组间差异无统计学意义,提示HIBD鼠学习记忆能力下降,EPO干预能减轻HIBD对海马学习记忆功能的损害。结论EPO对新生鼠缺氧缺血性脑损伤具有近期病理和远期功能保护作用,其机制与抑制细胞凋亡的发生有关。     

人EPO cDNA基因在CHO细胞中的稳定表达

建立稳定表达人红细胞生成素（ＥＰＯ）的工程细胞株。方法：用 ＤＮＡ磷酸钙共转染法,将人ＥＰＯ ｃＤＮＡ的表达质粒 ｐＣＤＢ与标志质粒 ｐＳＶ－ｄｈｆｒ共转染到 ＣＨＯ－ｄｈｆｒ－细胞中。用 ＥＬＩＳＡ法检测到 ７０个克隆的细胞培养上清,筛选出５０个克隆细胞系。结果：经ＭＴＸ加压扩增,获得４系高效表达ＥＰＯ的细胞系（Ｂ４、Ｃ３、Ｆ１０、Ｇ７）,表达量为 ２． ２～１０ μｇ／（１０６ ｃｅｌｌ· ２４ ｈ）,ＥＰＯ的分泌量在上述细胞系扩增了 １１～３１倍。 Ｆ１０细胞系表达量为最高,并进一步亚克隆纯化。其中Ｆ１０－６亚克隆细胞株的平均表达水平为１０ ｕｇ／（１０６ｃｅｌｌ·２４ ｈ）,细胞冻存后复苏传代１５次,ＥＰＯ的表达水平无明显改变。结论：以Ｆ１０－６亚克隆细胞株建立了工程细胞株。     

Measurement of erythropoietin in anephric children

Serum erythropoietin (Ep) levels were measured using a highly sensitive radioimmunoassay in 69 children undergoing chronic dialysis; 31 were anephric, whereas 38 were non-nephrectomized (nephric). Twenty-nine normal children were studied as controls. Serum Ep levels in the anephric group were much higher than anticipated (mean 19.7±1.8 mU/ml), albeit significantly lower than those measured in normal children (mean 26.2±2.4 mU/ml,P<0.05), or in nephric children on dialysis (33.0±2.9 mU/ml,P<0.001). Anephric children on peritoneal dialysis (PD) had significantly (P<0.05) higher serum levels of Ep (22.7±2.4 mU/ml,n=19) than anephric children on hemodialysis (HD) (15.1±2.3 mU/ml,n=12). There was no significant difference between Ep levels in anephric patients dialyzed for less than or equal to 1 year (19.6±2.0 mU/ml,n=20) compared with anephric patients dialyzed for more than 1 year (20.0±3.9 mU/ml,n=11). Although serum Ep levels showed a tendency to increase with time after nephrectomy, the mean values for <3 months (14.7±1.9), 3 months–12 months (21.0±2.7), and >12 months (21.6±6.0) were not significantly different from each other. This demonstration of relatively normal levels of serum Ep in anephric children suggests that extrarenal sites of Ep production are able to exert a significant response to severe anemia in patients who are devoid of renal parenchyma.Table of SPNSG centers and investigators, and source of patients studied: Offprint requests to: R. J. Hogg, Department of Pediatrics, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX, 75246, USA     

Red blood cell transfusions in newborn infants: Revised guidelines

In general, health care professionals taking care of high risk infants in neonatal intensive care units have become more restrictive in their use of red blood cell transfusion over the past 10 years. The present statement is intended for those caring for high risk newborn infants (preterm to one month of age). The objectives of this statement are to provide guidelines to reduce the incidence of anemia in preterm and term infants, to identify strategies to decrease the need for red blood cell transfusions and to limit donor exposure in this population. Recommendations for red blood cell transfusions are included.     

Kinetics of erythropoiesis in dialysis patients receiving recombinant erythropoietin treatment

In eleven patients with uraemia on intermittent haemodialysis treatment, recombinant human erythropoietin (rHuEpo) was used at a dosage schedule of 100 IU/kg bodyweight thrice weekly. Erythrokinetic studies (blood volume, RBC survival and iron kinetics) were performed in nine cases before and after 6 months of treatment. The remaining two patients had only RBC and plasma volume determinations before and after treatment. Although total blood volume remained unchanged, RBC volume was increased in all cases. Red cell loss was not modified, and quantitative improvement of RBC production was noted in all cases. No qualitative defect of erythroid maturation or release was observed in the treated patients. In conclusion, rHuEpo treatment improves the anaemia of haemodialysis patients by normalising circulating RBC volume only through an increase in red cell production.     

重组人促红细胞生成素对颅脑损伤患者的神经保护作用

目的评价促红细胞生成素用于颅脑损伤患者的临床意义。方法对两组条件相似的颅脑损伤患者共40例进行随机配对的前瞻性研究；其中治疗组于入院后24h开始使用重组人促红细胞生成素（rhEPO）；采用6000U／次，皮下给药，隔日1次共2w。对照组不给予rhEPO处理，其他处理同治疗组，高压液相色谱法（HPLC）测定两组患者脑脊液谷氨酸含量，并将两组的治疗结果进行对比分析。结果两组患者脑脊液谷氨酸含量及预后有明显差异，治疗组脑脊液谷氨酸含量低于对照组（P〈0．01），预后优于对照组（P〈0．01）。结论颅脑损伤患者使用rhEPO可减轻损伤后谷氨酸的兴奋性毒性作用，对颅脑损伤患者有神经保护作用。     

促红细胞生成素对急性脑损伤的保护作用

目的观察重组人促红细胞生成素(r-Epo)对大鼠急性脑损伤后脑细胞凋亡及脑水肿的影响。方法30只大鼠分为A、B、C 3组,B、C 2组用自由落体打击器制作脑外伤模型,C组r-Epo预处理,48 h后断头取脑。制作石蜡切片,TUNEL法检测细胞凋亡,同时用干湿重法测定各组大鼠脑组织含水量。结果与B组比较,C组外伤侧脑组织含水量明显降低(P<0.01),细胞凋亡数明显减少(P<0.01)。结论r-Epo能显著降低急性脑损伤后脑水肿,减少水肿区神经细胞凋亡,对急性损伤后脑组织有良好的保护作用。     

颅脑损伤患者血清促红细胞生成素的测定及其意义

目的:探讨急性颅脑损伤患者血清促红细胞生成素(EPO)含量与颅脑损伤程度的关系.方法:选择颅脑损伤120例,按损伤程度分轻、中、重三型,即颅脑损伤轻型组、中型组、重型组;选择30位健康武警战士作为对照组.均采用酶联免疫吸附法(ELISA法)检测血清EPO含量,并进行对比分析.结果:血清EPO含量:颅脑损伤轻型组、中型组与对照组比较差异具有非常显著的统计学意义(P＜0.01);重型组与对照组比较差异有显著性统计学意义(P＜0.05). 结论:急性颅脑损伤,尤其是轻、中型急性颅脑损伤可刺激机体产生EPO,EPO的含量可提示急性颅脑损伤的程度.     

Clinical and basal aspects of anemia during antiviral therapy for hepatitis C

Background and Rationale. Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated.Patients and methods. 44 chronic hepatitis C patients on interferon-ribavirin treatment were included. Anemia-related parameters were measured before and during treatment. Potential changes in membrane phospholipids composition of erythrocytes of patients on anti-viral treatment and potentially increased erythrocyte susceptibility to osmotic or bile salt induced stress were explored.Results. Anemia was almost universal during treatment, with evidence of hemolysis. Decrease of Hb after six months of therapy was 2.1 ± O.I mmol/L (range -0.6-4.1). Higher pre-treatment Hb, highest ribavirin dose (1S-17.S mg/kg) and lower pre-treatment platelet level were independent risk factors for decrease of Hb. Serum erythropoietin levels increased during treatment with negative correlation to Hb levels at week 12 (r = -0.70, p = 0.002) and 24 (r = -0.72, p = 0.002). Erythrocyte membrane phospholipid composition did not differ between anemic patients and healthy controls. Also, resistance to osmotic or bile salt induced stress was normal in anemic patients. Phosphatidylserine exposure at the outer membrane leaflet did not change upon 24 hrs ex vivo incubation with pharmacological ribavirin concentration.Conclusions. Anemia is almost universal during anti-HCV treatment. The extent of anemia correlates with pre-treatment levels of thrombocytes and Hb and with high ribavirin dosing. Although we found hemolysis as contributing factor, our data do not indicate that altered membrane phospholipids composition is an important factor in pathogenesis of anemia.