促红细胞生成素联合左旋肉碱对肾性贫血患者内皮素及左室重构临床研究

目的观察促红细胞生成素联合左旋肉碱对肾性贫血患者的疗效及对血清中内皮素（ET）的影响,以指导临床工作。方法收集我院尿毒症患者伴肾性贫血患者80例,将其随机分为观察组（40例）和对照组（40例）,对照组应用促红细胞生成素治疗,观察组应用促红细胞生成素联合左旋肉碱治疗,观察治疗后血红蛋白（Hb）、红细胞比容（HCT）、血浆内皮素（ET）、左心房内径（LAD）、左心室收缩末期内径（LVDs）、左心室舒张末期内径（LVDd）的变化。结果治疗前后的改变值观察组均明显高于对照组（P〈0.05）：Hb[（33.10±3.29）g/L vs（25.10±3.02）g/L]、HCT[（6.35±1.64）%vs（3.49±1.10）%]、ET[（107.10±19.62）pg/mL vs（52.32±10.54）pg/mL];观察组治疗后均明显低于治疗前（P〈0.05）：LAD[（32.54±3.62）mm vs（35.43±3.62）mm]、LVDs[（31.29±2.65）mm vs（34.15±3.61）mm]及LVDd[（54.23±3.86）mmvs（59.75±4.32）mm],对照组治疗前后比较,差异无统计学意义（P〉0.05）。结论促红细胞生成素联合左旋肉碱对肾性贫血患者的疗效明显,且能有效调节ET的水平,降低左室重构,在临床中可以积极应用。     

促红细胞生成素上调海马pCREB表达和改善脑缺血小鼠认知功能

目的: 探讨促红细胞生成素(EPO)对小鼠脑缺血所致的认知功能障碍和海马神经元损伤的保护作用及机制。方法: C57BL/6绿色荧光蛋白转基因小鼠随机分为假手术(sham)组、脑缺血/再灌注(I/R)组和EPO治疗组;采用双侧颈总动脉阻断(2-VO)方法复制小鼠全脑缺血模型,跳台实验测试小鼠学习记忆能力,Nissl染色检测海马神经元存活情况,Western blotting检测磷酸化cAMP反应元件结合蛋白(pCREB)表达水平,激光共聚焦显微镜和Neurolucida软件分析检测海马CA1区神经元形态及树突棘的变化。结果: 脑缺血导致小鼠学习记忆能力下降,海马CA1区神经元迟发性死亡和树突棘丢失;EPO治疗能显著提高脑缺血小鼠的学习记忆能力,减少脑缺血所致的海马CA1区神经元死亡和树突棘的丢失,显著上调海马CA1区神经元pCREB蛋白的表达。结论: EPO可能通过上调pCREB的表达来保护神经元损伤、防止神经元树突棘的丢失,进而改善脑缺血小鼠的认知功能。     

慢性马兜铃酸肾病大鼠贫血发生的机制

目的 探讨慢性马兜铃酸肾病（CAAN）贫血的发生机制。 方法 用62只SD大鼠筛查血红蛋白（Hb）,求正常值。随机选择24只Hb正常的大鼠,分为对照组及模型组,各12只,后者予关木通浸膏水溶液间断灌胃制作CAAN模型。在给药前及8周末,分别检测两组各6只大鼠体质量、Hb、尿蛋白量（24 h）及肌酐清除率（Ccr）,然后处死大鼠,留取肾组织做Masson染色观察肾间质纤维化程度;实时定量PCR法检测肾组织中红细胞生成素（EPO）mRNA表达;免疫组化染色观察肾组织中Ⅰ型胶原（ColⅠ）、氨基肽酶P（APP）、低氧诱导因子（HIF）1α及2α的蛋白表达。 结果 大鼠的正常Hb值为（155.9±16.5） g/L,低于123.6 g/L为贫血。给药前,对照组与模型组间各指标的差异均无统计学意义。8周末时,与对照组比较,模型组大鼠Hb和Ccr显著下降[（121.66±15.68） g/L比（169.00±12.89） g/L,（0.63±0.13） ml/min比（1.27±0.18） ml/min];尿蛋白量（24 h）显著增多[（27.04±9.40） mg/d比（6.11±0.84） mg/d];肾间质纤维化相对面积及ColⅠ相对面积显著增加[（12.89±2.33）%比（0.55±0.10）%,（13.92±2.92）%比（1.32±0.84）%];肾组织APP蛋白表达和EPO mRNA表达显著下调 [（0.55±0.23）%比（3.77±1.06）%,0.005±0.001比0.032±0.013];HIF-1α和HIF-2α蛋白表达显著上调 （2.55±0.16比1.12±0.46,2.33±0.33比1.15±0.27）（均P < 0.01）。 结论 CAAN的贫血发生可能与肾小管周毛细血管毁坏所导致的EPO产生减少有关,虽然HIF表达已代偿性增强,但仍未能阻止贫血发生。     

红细胞生成素对高糖诱导下肾小管上皮细胞转分化的影响

目的 探讨红细胞生成素（EPO）对高糖诱导下的肾小管上皮细胞转分化的影响。 方法 体外培养人肾小管上皮细胞株（HK-2细胞）,分为正常对照组、渗透浓度对照组、高糖组、高糖＋EPO（5 U/ml）组和高糖＋EPO（10 U/ml）组。RT-PCR法检测各组细胞α平滑肌肌动蛋白（α-SMA）、转化生长因子β1（TGF-β1）、Smads信号蛋白2（Smad2）及整合素连接激酶（ILK）的mRNA表达。细胞免疫荧光法检测细胞TGF-β1及α-SMA的蛋白表达。 结果 RT-PCR结果显示,相对于对照组,高糖组细胞α-SMA、TGF-β1、Smad2、ILK的mRNA表达均显著上调（P ＜ 0.01）。细胞免疫化学也显示,高糖组TGF-β1和α-SMA的蛋白表达较对照组显著上调（P ＜ 0.01）,而高糖＋EPO（5 U/ml）组和高糖＋EPO（10 U/ml）组上述指标的表达均显著低于高糖组（均P ＜ 0.01）。 结论 EPO能抑制高糖诱导的肾小管上皮细胞转分化,可能与其抑制TGF-β1、Smad2及ILK表达有关。     

The protective effect of erythropoietin infusion on testicular torsion/detorsion: an experimental study

Introduction  The aim of the present study was to evaluate the effects of erythropoietin (EPO) on the histopathology of testes after unilateral testicular torsion and detorsion. Materials and methods  Twenty-five male Sprague–Dawley rats weighing 120 g were used in this study. The rats were randomly divided into three groups, a sham group consisting of five rats and the other two groups consisting of ten rats. In group 1 (sham group), right orchiectomy with no additional intervention was performed. In group 2 (T/D group), torsion was created by rotating the testis 720° in a clockwise direction for 4 h. After a 4-h torsion period, the right testis was detorted and replaced into the scrotum for 4 h. After the torsion, 0.5 cc 0.9% NaCl solution was injected once and three times in a week (total 12 doses). In group 3 (T/D + erythropoietin; EPO group), the same surgical procedure was done as in group 1, but EPO 1,000 IU/kg was injected just before the detorsion and three times in a week. At the end of each procedure, bilateral orchiectomies were performed for the histopathological examinations in all groups. Results  We examined the testes weight, vascularization of the region between the seminiferous tubules, percentage of necrotic seminipherous tubules, and maturation of spermatogenesis in terms of necrosis, sertoli cells, maturation arrest of spermatogenesis, hypospermatogenesis, and normal spermatogenesis of torsioned testis tissues with and without EPO treatment. Extremely significant differences in testicular weight were observed in group 1 compared to groups 2 and 3 (P < 0.001). Conclusion  Administration of EPO significantly influenced the rescue of testicular function by preserving the intact seminiferous tubular morphology, lowering the percentage of necrotic seminipherous tubules, and significantly reducing histological damage (P < 0.05).     

Hemoglobin target in chronic kidney disease: a pediatric perspective

Erythropoietin has transformed the treatment of the anemia of chronic kidney disease (CKD) by preventing the need for blood transfusions and improving the quality of life in all patients, including children. Anemia in children, in the age group 1–19 years, may be defined as hemoglobin (Hgb) levels < 12.1–13.5 g/dl for boys and < 11.4–11.5 g/dl for girls, based on the National Health and Nutrition Examination Survey (NHANES) norms. The prevalence of anemia in children ranges from 31.2% in stage 1 CKD to 93.3% in stages 4 and 5 CKD. The recent publication of trials evaluating the optimal hemoglobin level in adult CKD patients has generated considerable uncertainty about the target Hgb level in children with CKD. It is unclear whether generalizing of results from these trials in adults to children is appropriate. Adequately powered, randomized, controlled studies have not been conducted on children, and none to our knowledge are currently planned. The Food and Drug Administration (FDA) offers scant guidance on the Hgb target level for children, other than implying that it should be no different from that for adults. The purpose of this editorial is to critically scrutinize whether there is a benefit to the normalization of anemia in children with CKD and whether adoption of the results from adult studies is appropriate.     

蔗糖铁注射液联合红细胞生成素治疗肾性贫血的临床观察

目的 观察蔗糖铁注射液联合红细胞生成素治疗伴有缺铁的维持性血液透析肾性贫血患者疗效及安全性.方法 选取尿毒症维持性血液透析患者46例,按随机数字表法分为治疗组(26例)和对照组(20例).治疗组采用静脉滴注蔗糖铁100 mg,每周2次,总量达1000 mg改为100 mg,每周1次;对照组采用口服乳酸亚铁0.2 g,每日3次.红细胞生成素的使用剂量和方法两组相同,总疗程均为10周.结果 经治疗后治疗组患者血红蛋白、红细胞压积、血清铁蛋白水平与对照组比较差异有统计学意义(P<0.05).结论 蔗糖铁联合红细胞生成素治疗肾性贫血疗效优于口服铁剂联合红细胞生成素治疗.不良反应发生率更低,可作为肾性贫血患者长期补铁的方法之一.     

Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

AIM： TO investigate the effect of exogenous erythro- poietin （EPO） administration on acute lung injury （ALI） in an experimental model of sodium taurodeoxycholate- induced acute necrotizing pancreatitis （ANP）. METHODS： Forty-seven male Wistar albino rats were randomly divided into 7 groups： sham group （n = 5）, 3 ANP groups （n = 7 each） and 3 EPO groups （n = 7 each）. ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum arnilase, IL-2, IL-6 and lung tissue malondialdehyde （MDA） were measured. Pleural effusion volume and lung/body weight （LW/BW） ratios were calculated. Tissue levels of TNF-a, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored.RESULTS： The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-（~ （TNF-（~） and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters a~er exogenous EPO administration, particularly at 48 h and 72 h. CONCLUSION： EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte （PMNL） accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore     

Stimulating erythropoiesis in inflammatory bowel disease associated anemia

Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.     

The pharmacokinetic profile of recombinant human erythropoietin is unchanged in patients undergoing cardiac surgery

Background

In anticipation of future studies, we examined the pharmacokinetics profile of erythropoietin (EPO) in patients undergoing cardiac surgery.

Methods

Cardiac surgical patients were enrolled into one of six groups: four cardiopulmonary bypass (CPB) groups [placebo (n?=?6), 250 IU/kg EPO (n?=?3), 500 IU/kg EPO (n =?3), and 500 IU/kg EPO, two doses (n =?6)] and two off-pump coronary artery bypass (OPCAB) groups [placebo (n?=?3) and 500 IU/kg EPO (n?=?3)]. The EPO was administered prior to anesthesia and 10 min after CPB (if required). Blood samples for serum EPO were collected at baseline, 10 min after dosing, 5 min after sternotomy, during CPB or the equivalent for OPCAB (5, 15, 45, 60 min), and post-CPB (5, 15, 45, and 60 min, 6, 12 and 24 h, and daily until day 5).

Results

Endogenous EPO increased within 24 h of surgery in the placebo group and remained elevated. There was approximately a 40% decrease in serum EPO concentration at the initiation of CPB due to an increase in circulatory blood volume. There were no differences in apparent volume of distribution in the plasma (Vc) (42.2?±?9.9, 39.8?±?6.3, 42.3?±?14.0 mL/kg), clearance (CL) (4.63?±?1.14, 3.44?±?0.68, 4.27?±?0.52 mL h/kg), and t_½ (16.4?±?8.0 16.9?±?10.6, 22.4?±?9.3 h) between the CPB treatment groups. The pharmacokinetic profile of EPO in the OPCAB group was similar to that for the CPB groups: Vc = 39.3?±?7.0 mL/kg, CL = 4.98?±?0.17 mL h/kg and t_½ = 17.1?±?18.1 h.

Conclusions

CPB had no apparent effect on the pharmacokinetics of EPO.