慢性肾功能衰竭贫血患者红细胞分布宽度与促红细胞生成素水平的相关性研究

目的 探讨慢性肾功能衰竭(CRF)贫血患者红细胞分布宽度(RDW)与其红细胞生成素(EPO)水平的相关性.方法 将76例CRF贫血患者分为RDW≥13.0％组(n=43)和RDW＜13.0％组(n=33),用免疫学方法和生物检测技术测定CRF患者EPO、血色素、白蛋白、血清铁等指标,并对结果进行统计分析.结果 RDW≥13.0％组肾性贫血患者的EPO水平较RDW＜13.0％组相对低[O/P比值:(0.351±0.12)vs.(0.167±0.57),P＜0.01],并且RDW与血清Alb、Fe水平呈负相关(r=-0.42,-0.37).结论 RDW可以作为监测CRF贫血患者EPO水平的预测指标,高水平的RDW提示CRF患者EPO水平相对较低.     

促红细胞生成素对慢性肾衰竭贫血患者骨髓超微结构的影响

目的 探讨促红细胞生成素(EPO)对慢性肾衰竭(CRF)贫血患者骨髓超微结构的影响.方法 对23例CRF贫血患者给予重组人红细胞生成素(rhEPO)100 U/kg,每周3次,并进行常规血液透析,于治疗前及治疗12周后检测血常规,观察骨髓超微结构改变情况.结果 治疗后血红蛋白、血细胞比容、网织红细胞和血小板较治疗前均升高(P＜0.05,P＜0.01);骨髓造血微环境恢复,三系各阶段血细胞超微结构恢复正常.结论 EPO是治疗CRF贫血的决定性生长因子.     

促红素加福乃得治疗慢性肾衰贫血的临床观察

目的 探讨重组促红细胞生成素(EPO)治疗慢性肾衰(CRF)贫血患者的疗效.方法 对50例因CRF行血液透析治疗伴贫血的患者于血透结束时皮下注射EPO,配合福乃得治疗,作前后对比.结果 患者治疗后红细胞压积(Hct)及Hb显著上升(P＜0.01),其中显效30例(60%);有效17例(34%);无效3例(6%);总有效率达94%.结论 EPO配合福乃得治疗CRF贫血疗效确切.     

慢性肾衰血透患者对红细胞生成素疗效与C-反应蛋白关系的研究

目的为了解慢性肾衰竭(CRF)血透患者对红细胞生成素(EPO)治疗贫血的疗效与C-反应蛋白(CRP)之间的关系.。方法对血液透析稳定、充分,伴有贫血的60例患者,排除缺铁、感染、继发性甲旁亢后,测定CRP、血清白蛋白、血常规,同时使用EPO,3 000 U皮下注射,2次/周,观察疗程12周。比较CRP升高组与CRP正常组患者上述参数治疗前后的变化。结果CRF患者中19例(31.6%)CRP升高,经EPO治疗后血红蛋白、红细胞压积、血清白蛋白与治疗前相比差异不显著(P>0.05),CRP正常组治疗后各项参数与治疗前相比差异显著(P〉0.05)。结论慢性肾衰竭患者较普遍存在慢性炎症状态,并伴随着低白蛋白血症,CRP升高也是EPO抵抗的原因之一。     

槲皮素对大鼠慢性肾功能衰竭及促红细胞生成素水平的影响

目的:探讨腺嘌呤诱导大鼠慢性肾功能衰竭(CRF)模型的特点及中药成分槲皮素对CRF的作用及对促红细胞生成素(EPO)水平的影响.方法:以喂饲0.75%腺嘌呤制成大鼠CRF模型后,灌胃给予槲皮素100 mg·kg-1·d-1,共喂药8周,观察治疗组与肾衰组病理变化,测定大鼠肾功能、肾组织羟脯氨酸及血浆和肾组织EPO含量.结果:治疗组肾组织病理损害明显轻于肾衰对照组;血浆BUN、Scr、肾组织羟脯氨酸含量明显下降(P＜0.01);血浆和肾组织中EPO的含量均明显升高(P＜0.01).结论:槲皮素对防治CRF有显著效果并能有效提高CRF时血浆及肾组织中EPO含量及减轻肾间质纤维化.     

促红细胞生成素对慢性肾衰竭内分泌紊乱调节作用研究进展

慢性肾衰竭(CRF)患者由于体内毒素的蓄积等可出现一系列内分泌功能紊乱.促红细胞生成素(EPO)是目前临床广泛应用于纠正贫血的药物.近年随着研究的不断深入,人们发现EPO可通过其改善贫血及非纠正贫血作用间接或直接调节CRF的内分泌功能紊乱.现将就这方面内容做一综述.     

肾性贫血成因及综合治疗

肾性贫血为正常色素性正细胞性贫血，是由多种因素引起的红细胞生成减少、损耗、丢失过多等原因造成。具体原因：(1)EPO(促红细胞生成素)的相对或绝对不足是引起肾性贫血的基本原因，CRP病人肾组织已严重损伤。正常组织明显减少，故合成EPO的细胞数量减少或分化增殖障碍，或这些组织合成EPO能力下降，导致肾性贫血。(2)尿毒症毒素影响细胞的生存时间，测定结果表明CRF     

人参养荣汤治疗CRF贫血大鼠的实验研究

目的:探讨人参养荣汤治疗CRF大鼠贫血的机理。方法:0.5%腺嘌呤和4%酪蛋白饲料喂养制作CRF贫血模型,给药4周后检测大鼠血红蛋白,测定红细胞脆性,ELISA法检测CRF大鼠血清EPO含量,观察肾脏病理变化。结果:人参养荣汤显著提高CRF贫血大鼠的血红蛋白量和血清EPO水平,能改善红细胞脆性,改善肾脏病理。结论:人参养荣汤可能通过提高血清EPO含量、改善肾脏病理来纠正CRF大鼠的贫血状态。     

应用促红细胞生成素治疗慢性肾衰贫血的临床观察

慢性肾功能衰竭(简称CRF,后同)的贫血虽与许多因素有关,但其中促红细胞生成素(EPO)相对不足或生成减少,与CRF贫血关系最密切,且为最难矫正的因素。     

促红素临床应用的进展

促红素(EPO)是由与近侧肾小管邻近并作为肾对氧敏感反应装置的细胞合成的一种糖蛋白的生长因子,可能是一种血红素蛋白。在骨髓中,EPO能结合到原始红细胞上并活化其上的特异性受体。由于这种EPO-受体复合物的存在,原始细胞继续它们预定的发展过程成为成熟的红细胞,如果无EPO-受体复合物,则原始细胞将崩溃及死亡。在正常稳定状态下,血浆中EPO浓度为10～20U/L(约2 pmol/L)即可诱导产生足量的红细胞以取代衰老的红细胞,并可保持到达肾氧感受器的足够氧流量,以保证基础水平EPO合成。在贫血时肾氧流量降低可指数性地增加EPO合成,因此在红细胞     

睾酮对慢性肾功能衰竭大鼠肾性贫血的影响及其作用机制

目的 研究睾酮对慢性肾功能衰竭大鼠肾性贫血的治疗效果并探讨其作用机制.方法 24只雄性Wistar大鼠采用随机单位组设计组法分为:对照组(NC)、正常大鼠睾酮干预组(NT)、慢性肾功能衰竭大鼠组(CD)、慢性肾功能衰竭大鼠睾酮治疗组(CT).CD、CT两组建立慢性肾功能衰竭大鼠模型,造模成功后NT、CT两组给予丙酸睾酮皮下注射,8周后处死大鼠,检测贫血指标及铁调素,促红细胞生成素(EPO)表达情况.结果 睾酮能显著升高慢性肾功能衰竭大鼠血红蛋白(Hb),血清铁(SI),总铁蛋白结合力(TIBC)表达,同时增加肾脏EPO的表达,降低肝脏内铁调素表达.结论 睾酮能显著纠正慢性肾功能衰竭大鼠肾性贫血,其机制可能与上调EPO表达、减弱铁调素作用相关.     

表达人红细胞生成素裸质粒治疗肾性贫血的实验研究

目的：观察表达人红细胞生成素(EPO)基因裸质辛立通过电脉冲转移法导入大鼠和猕猴体内治疗腺嘌呤所致的肾性贫血的效果。方法：实验选择了喂含腺嘌呤饲料所致大鼠和猕猴的肾性贫血模型，电脉冲转移法把质粒导入动物股四头肌。实验分正常组、模型组、表达大鼠EPO基因裸质粒对照组(仅在大鼠肾性模型中)和不同剂量表达人EPO基因裸质粒组。动态检测血细胞比容(HCT)水平；提取给药部位肌肉组织总RNA进行逆转录PCR，检测EPO基因在肌细胞当中的表达；用EPO酶联免疫(ELISA)试利盒测定血清EPO水平。结果：电脉冲肌肉转移表达EPO裸质粒可在局部有效表达和分泌。在大鼠模型中，给药后第2～5周，表达大鼠EPO基因裸质粒对照组和表达人EPO基因裸质粒组的HCT水平明显高于模型组。在猕猴模型中，表达人EPO基因裸质粒组在给药后第4～5周HCT水平明显高于模型组。在大鼠模型中，表达人EPO基因裸质粒组的血清有明显的中和活性，可抑制BEF-2细胞的增殖。结论：电脉冲转移表达EPO基因裸质粒对腺嘌呤所致猕猴肾性贫血和大鼠肾性贫血具有明显的治疗作用。     

慢性肾衰患者促红细胞生成素与血红蛋白的相关性研究

目的探讨慢性肾衰（CRF）贫血患者血清促红细胞生成素（sEPO）与血红蛋白（Hb）的关系。方法20例慢性肾衰贫血患者，采用放射免疫法测定其血清促红细胞生成素（Serum erythropoietin，sEPO）的水平，分析sEPO与Hb的相关性；同时以缺铁性贫血（IDA）患者的sEPO对贫血的反应作为贫血状态下sEPO对Hb正常相关关系的对照，测定20例IDA患者的sEPO，并进行相关回归分析。结果20例慢性肾衰贫血组的sEPO水平明显低于IDA患者（P〈0．001）。慢性肾衰贫血组及IDA组的Hb与sEPO均呈明显的直线负相关关系（rIDA=-0.458，PIDA〈0.005；rCRF=-0．226，PCRF〈0．05）。慢性肾衰贫血组Hb—sEPO回归直线的斜率（bCRF=-0．0123）与在Y轴上的截距（aCRF=1．98）均小于IDA组（bIDA=-0．0183，aIDA=2．797）。结论慢性肾衰贫血患者普遍存在sEPO相对缺乏，表现为sEPO对贫血反应迟钝。     

Dual Therapeutic Effects of an Albumin-Based Nitric Oxide Donor on 2 Experimental Models of Chronic Kidney Disease

Chronic kidney disease (CKD) is accompanied by a variety of complications, typically renal anemia and kidney fibrosis. Accordingly, it is desirable to develop the novel therapeutics that can treat these CKD conditions. Since nitric oxide (NO) has multiple functions including hypoxia inducible factor stabilizing, anti-inflammatory, anti-oxidative, and anti-apoptoic activities, the use of NO for the CKD therapy has attracted considerable interest. Here, we evaluate the therapeutic impacts of S-nitrosated human serum albumin (SNO-HSA), a long-lasting NO donor, on 2 animal models of CKD. SNO-HSA increased the expression of erythropoietin (EPO), VEGF, and eNOS by stabilizing hypoxia inducible factor–1α in HepG2 and HK-2 cells. SNO-HSA increased hematopoiesis in both healthy and renal anemia rats, suggesting the promotion of EPO production. In unilateral ureteral obstruction–treated mice, SNO-HSA ameliorated kidney fibrosis by suppressing the accumulation of renal extracellular matrix. SNO-HSA also inhibited unilateral ureteral obstruction–induced α–smooth muscle actin increase and E-cadherin decrease, suggesting that SNO-HSA might suppress the accumulation of myofibroblasts, an important factor of fibrosis. SNO-HSA also inhibited the elevations of fibrosis factors, such as transforming growth factor–β, interleukin-6, and oxidative stress, while it increased EPO production, an anti-fibrosis factor. In conclusion, SNO-HSA has the potential to function as a dual therapeutics for renal anemia and kidney fibrosis.     

Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys

 Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells. Received: 2 May 1996/Accepted: 29 May 1996     

促红细胞生成素对慢性肾衰竭贫血患者骨髓祖细胞的影响

目的 观察促红细胞生成素(EPO)对慢性肾衰竭(CRF)贫血骨髓祖细胞的影响,探讨CRF血液系统改变及EPO治疗机制.方法 对20例CRF贫血采用国产济脉欣(EPO)3000～6000 U,皮下注射,每周3次,于治疗前及连续治疗12周后在髂后上棘同一部位行骨髓穿刺抽取等量骨髓液,观察EPO治疗前后血常规和骨髓祖细胞变化情况.结果 治疗后血红蛋白、血细胞比容、白细胞及血小板升高,而血清肌酐下降,与治疗前比较差异有统计学意义(P<0.01).骨髓红系造血祖细胞(CFU-E)、粒-单系祖细胞(CFU-GM)、成纤维祖细胞(CFU-F)集落数较治疗前均明显增多,差异均有统计学意义(P<0.01).骨髓CFU-F集落产率与CFU-E和CFU-GM集落产率呈正相关(r=0.32,r=0.49,P＜0.05).结论 EPO治疗CRF贫血可使骨髓造血微环境恢复,保护造血干细胞,并恢复其自我复制、增殖与分化.     

EPO tecting the endothelium

Erythropoietin is a 30.4 kDa protein that is produced and secreted from the kidney in response to anemia and hypobaric hypoxia. Binding of EPO to its receptor (EPO-R) on bone marrow-derived erythroid progenitor cells results in the stimulation of red blood cell production. Evidence is accumulating however, that the biological effects of recombinant EPO therapy extend beyond the stimulation of erythropoiesis. The discovery that the EPO-R is expressed on vascular endothelial cells suggests that the vasculature may be a biological target of EPO. Indeed, several studies have now demonstrated that the protective effect of EPO administration involves the activation of the protein kinase B/Akt pathway which can protect cells from apoptosis. Future work is likely to provide further insight into the mechanisms by which EPO protects vascular endothelial cells from injury and give us a better understanding of the pharmacological doses that are required to achieve this protection.     

New alternatives for erythropoietin therapy in chronic renal failure

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.     

促红细胞生成素对慢性肾功能衰竭大鼠肾功能的影响

目的:研究促红细胞生成素(EPO)对慢性肾功能衰竭(CRF)大鼠肾功能的影响及其作用机制.方法:将5/6肾切除大鼠随机分为3组:Ⅰ组为假手术组;Ⅱ组为CRF组;Ⅲ组为给予促红细胞生成素的CRF组.第2次术后8周检测各组血压、尿蛋白、血清尿素氮、血肌酐、血红蛋白;观察肾组织病理改变,检测血清及肾组织中血红蛋白氧合酶 1(HO 1)活性;用免疫组化方法检测HO 1在肾脏中的表达.结果:Ⅲ组与Ⅱ组比较,血压、尿蛋白、血肌酐及尿素氮水平明显降低(P＜0.05),肾小球系膜增生及间质纤维化程度明显减轻(P＜0.05);HO 1活性检测显示,Ⅲ组大鼠血清中HO 1活性明显高于Ⅱ组(P＜0.05),免疫组化显示Ⅲ组大鼠肾组织中HO 1表达明显高于Ⅱ组(面密度、平均光度)(P＜0.05).结论:EPO使CRF大鼠肾功能得到改善,并使CRF大鼠血清及肾组织中HO 1表达及活性明显升高.     

三黄肾康丸治疗大鼠慢性肾衰的实验研究

目的 :观察三黄肾康丸对腺嘌呤致大鼠慢性肾衰 (CRF)的影响。方法 :连续喂养0 75 %腺嘌呤使Wister大鼠产生类似于人慢性肾衰的症状。2周后 ,治疗组大鼠每天用中药三黄肾康丸 (12 0g/kg、6.0g/kg)灌胃 ,连续6周 ,并于第4、8周测定大鼠血尿素氮 (BUN )、肌酐 (Scr)、RBC、HGB、HCT及肾脏病理学检查。结果 :三黄肾康丸明显改善大鼠肾衰的症状 ,与模型组大鼠比较 ,肾重量减轻 (P<0 01) ,纤维化程度降低 ,肾组织内结晶沉积物减少。结论 :三黄肾康丸对大鼠肾衰有明显治疗效果