促红细胞生成素对急性肾衰竭的保护作用研究进展

近年来寻找修复和治疗急性肾衰竭的生物活性物质成为研究的热点。促红细胞生成素（EPO）是一种糖基化蛋白类激素,以往研究认为,EPO的主要生物学作用为促进红系祖细胞分裂分化成成熟的红细胞,增加循环中红细胞的数量,EPO被用于治疗慢性肾衰竭贫血已有20余年,直到最近几年的研究发现,促红细胞生成素具有纠正贫血以外的肾脏保护作用,它通过促进肾小管上皮细胞的再生,抑制其凋亡等多种途径,可以加快急性肾衰竭的修复,保护肾功能。     

促红细胞生成素对缺血再灌注心肌损伤保护作用的研究进展

<正>促红细胞生成素(erythropoietin,EPO)由肾脏产生,传统认为EPO主要用于手术、外伤、肿瘤等原因造成的贫血的治疗。但近年研究发现,EPO具有多种非造血功能,如抗凋亡、促血管生成、调节炎症和改善微循环等。除此之外,EPO对细胞也有一定的保护作用,本文就EPO对缺血再灌注心肌细胞保护作用的研究进展综述如下。1 EPO与EPO受体EPO是一种由165个氨基酸组成的糖蛋白,相对     

促红细胞生成素在心血管疾病中的应用进展

促红细胞生成素是一种造血细胞生长因子,主要用于治疗多种原因所致的贫血,最近的研究表明其具有多种非促造血方面的细胞保护作用,包括抗细胞凋亡、促血管生成作用等,可在心脏缺血损伤、心力衰竭等心血管疾病中发挥心肌细胞、组织的保护作用,从而为心血管疾病的治疗提供广阔前景。     

促红细胞生成素及其衍生物的心脏保护作用

促红细胞生成素(EPO)能直接促进红细胞生成,可用于预防和治疗多种原因引起的贫血.EPO广泛分布于人体各个系统,除促造血作用外,还具有抗炎、抗凋亡、促进新生血管生成等多种作用,并可通过这些作用发挥广泛的组织保护效能.然而,长期大剂量应用EPO必然增加高血压、血栓形成等风险.氨甲酰化促红细胞生成素(carbamylate...     

促红细胞生成素与心血管疾病

新近研究认为促红细胞生成素是一作用广泛的细胞保护剂,体内许多器官和组织包括心脏都表达促红细胞生成素及其受体,它可以减轻缺血缺氧时心肌细胞的损伤,减少心肌细胞的凋亡和促进新生血管生成,从而使其可能成为心血管疾病的治疗方法。     

促红细胞生成素与心肌缺血性疾病的研究进展

促红细胞生成素是一种造血细胞生长因子,主要用于治疗多种原因所致的贫血,最近的研究表明其具有多种非促造血方面的细胞保护作用,包括抗细胞凋亡、促血管生成作用等,可在心脏缺血性疾病中发挥心肌细胞保护作用,这些作用可能是其能治疗心血管疾病的治疗学基础。     

心力衰竭与贫血相关性研究进展

贫血在心力衰竭患者中有很高的发生率,其发病机制与血液稀释、铁缺乏、营养不良、慢性肾脏疾病、炎症性免疫激活、血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂的应用等因素有关。贫血与充血性心力衰竭患者的临床预后密切相关,并被认为是心力衰竭患者临床预后不良的独立因子。使用促红细胞生成素成为治疗充血性心力衰竭性贫血的新靶点,但也存在一定的风险。     

促红细胞生成素衍生物研究进展

促红细胞生成素（EPO）除了具有造血活性外,还具有抗凋亡等广泛的组织保护活性。近年来的研究发现促红细胞生成素衍生物———氨甲酰化促红细胞生成素（CEPO）,不表现任何促红细胞生成活性,不能与经典促红细胞生成素受体（EPOR）结合,但可通过新发现的一种受体EPOR-βcR（由EPOR和βcR形成的异源二聚体）起到与EPO类似的组织保护作用。与EPO不同,CEPO无明显的造血活性,CEPO的抗凋亡保护作用与其改善组织重塑及抑制瘢痕形成有关。     

促红细胞生成素的心脏保护作用

促红细胞生成素（erythrolooietin，EPO）不只限于治疗多种原因所造成的贫血，研究已经证明，EPO及其受体在心血管系统有广泛表达，通过对缺氧的调节、抗氧化、增强细胞抗凋亡能力、促进血管生成、抗炎等多种作用机制参与心肌保护。EPO的心脏保护作用机制综述如下。     

促红细胞生成素在慢性心力衰竭的临床应用及机制研究进展

促红细胞生成素是特异性作用于红系祖细胞的造血生长因子,但新近有证据表明,促红细胞生成素具有重要的心脏保护功能。动物实验显示：促红细胞生成素能改善左心室功能,促红细胞生成素能明显降低心肌细胞凋亡,促红细胞生成素能抑制血管内皮细胞发生凋亡,刺激内皮前体细胞有丝分裂,使用促红细胞生成素治疗合并贫血的慢性心力衰竭患者,可显著改善患者的心功能及临床症状。临床研究表明促红细胞生成素可明显提高慢性心力衰竭合并贫血患者的血红蛋白浓度,改善心功能,提高运动耐量,尽管促红细胞生成素在治疗肾性贫血过程中可能有导致血压增高、血栓形成的危险,但促红细胞生成素治疗心肌缺血和慢性心力衰竭是安全的。目前,对促红细胞生成素的应用,有可能开辟治疗慢性心力衰竭的新途径。但促红细胞生成素用于慢性心力衰竭的预后的影响还需在经过精确设计的前瞻性研究中进行检测,其长期治疗心脏的不良反应有待进一步探讨及促红细胞生成素起始治疗时间、选用以及血红蛋白浓度的靶目标也尚需进一步探讨。其作用机制尚待进一步探讨。     

促红细胞生成素治疗急性心肌梗死的研究进展

促红细胞生成素不仅能够促进红系分化增殖、促进造血,还具有更为重要的细胞保护作用,其受体广泛存在于心血管系统,在心脏的心外膜和心包膜均有表达。促红细胞生成素在心血管系统的作用越来越受到医学界的关注,尤其是促红细胞生成素对急性心肌梗死、缺血/再灌注损伤的心肌保护作用。     

Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor.

The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.     

The cardiovascular effects of erythropoietin

Erythropoietin is a hypoxia-induced hormone that is essential for normal erythropoiesis. The production of recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia associated with chronic renal failure and chemotherapy, and has been used as prophylaxis to prevent anemia after surgery. The erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes. Epo has potentially beneficial effects on the endothelium including anti-apoptotic, mitogenic and angiogenic activities. On the other hand, some reports suggest that rHuEpo may have pro-thrombotic or platelet-activating effects. Hypertension develops in 20-30% of renal patients treated with rHuEpo. Many patients with heart failure have anemia. Despite some potential adverse effects, early studies in heart failure patients with anemia suggest that rHuEpo therapy is safe and effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Further studies are warranted to define the role of rHuEpo in chronic heart failure and other cardiovascular settings.     

Urotensin-II and cardiovascular diseases

Urotensin-II (U-II) is a vasoactive factor with pleiotropic effects. U-II exerts its activity by binding to a G-protein-coupled receptor termed UT. U-II and its receptor are highly expressed in the cardiovascular system. Increased U-II plasma levels have been reported in patients with cardiovascular disease of varying etiologies. We and others have shown that U-II and UT expression is elevated in both clinical and experimental heart failure and atherosclerosis. U-II induces cardiac fibrosis by increasing fibroblast collagen synthesis. In addition, U-II induces cardiomyocyte hypertrophy and increased vascular smooth muscle cell proliferation. We have shown that U-II antagonism using a selective U-II blocker, SB-611812, attenuates cardiac dysfunction by decreasing cardiomyocyte hypertrophy and cardiac fibrosis. We have also shown that SB-611812 reduces neointimal thickening and increases lumen diameter in a rat restenosis model of carotid artery angioplasty. These findings suggest an important role for U-II in cardiovascular dysfunction and remodeling.     

The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome

Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) excessive cytokine production in CHF, which can cause both depression of erythropoietin production in the kidney and depression of erythropoietin response in the bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. It appears that iron deficiency is very common in CHF and is rarely recognized or treated. The iron deficiency can cause a thrombocytosis that might contribute to cardiovascular complications in both CHF and CKD and is reversible with iron treatment. Thus, attempts to control this anemia in CHF will have to take into consideration both the use of both Erythropoiesis Stimulating Agents (ESA) such as EPO and oral and, probably more importantly, intravenous (IV) iron. Many studies of anemia in CHF with ESA and oral or IV iron and even with IV iron without ESA have shown a positive effect on hospitalization, New York Heart Association functional class, cardiac and renal function, quality of life, exercise capacity and reduced Beta Natriuretic Peptide and have not demonstrated an increase in cardiovascular damage related to the therapy. However, adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed and are currently being carried out.     

The vitamin D system: a crosstalk between the heart and kidney

Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25‐dihydroxyvitamin D) by the 25‐hydroxy vitamin D 1‐hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin–angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD‐MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD‐MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.     

Beneficial effects of GH replacement therapy in adults

Growth hormone deficiency in adults is associated with psychosocial maladjustment, reduced muscle strength, and reduced exercise capacity. Body composition is significantly altered, with increased fat and decreased muscle volume as compared with healthy subjects. Kidney function is subnormal. Epidemiological data suggest premature mortality owing to cardiovascular disease in hypopituitary patients. Short-term GH treatment trials have shown improved psychosocial performance, normalization of body composition, increased muscle strength, improved exercise capacity, increased cardiac performance, and normalization of kidney function. Thus GH replacement therapy in GH-deficient adults exhibits potential long-term beneficial effects. A number of important questions have to be addressed before long-term GH replacement therapy in GH-deficient adults can be considered on a routine basis.     

Pathophysiology of anemia and erythrocytosis

An increasing understanding of the process of erythropoiesis raises some interesting questions about the pathophysiology, diagnosis and treatment of anemia and erythrocytosis. The mechanisms underlying the development of many of the erythrocytoses, previously characterised as idiopathic, have been elucidated leading to an increased understanding of oxygen homeostasis. Characterisation of anemia and erythrocytosis in relation to serum erythropoietin levels can be a useful addition to clinical diagnostic criteria and provide a rationale for treatment with erythropoiesis stimulating agents (ESAs). Recombinant human erythropoietin as well as other ESAs are now widely used to treat anemias associated with a range of conditions, including chronic kidney disease, chronic inflammatory disorders and cancer. There is also heightened awareness of the potential abuse of ESAs to boost athletic performance in competitive sport. The discovery of erythropoietin receptors outside of the erythropoietic compartment may herald future applications for ESAs in the management of neurological and cardiac diseases. The current controversy concerning optimal hemoglobin levels in chronic kidney disease patients treated with ESAs and the potential negative clinical outcomes of ESA treatment in cancer reinforces the need for cautious evaluation of the pleiotropic effects of ESAs in non-erythroid tissues.