促红细胞生成素对缺血再灌注心脏的心肌保护作用
3 临床应用前景
目前已通过基因重组技术人工合成了重组人促红细胞生成素(Recombinant human Erythropoietin.rhEPO),它的氨基酸顺序及生物学活性与天然EPO完全一致。rhEPO已成为治疗肾性贫血的首选药物,对肿瘤化疗所致贫血,及其他贫血性疾病都有良好效果。对于临床应用rhEPO治疗贫血的剂量、疗程及并发症目前已经为广大临床医生熟知,但用于组织保护和抗凋亡也还停留在实验室阶段。Shi Y[14]等仅只是在观察老鼠心肌缺血再灌注实验时发现1.0 U/ml的EPO是令心功能最大限能恢复的最佳浓度。为了避免如高血压、红细胞增多症、血栓形成等EPO应用所产生的并发症,Erbayraktar[15]等人通过缩短EPO 的半衰期来达到预期的目的。他们在EPO对神经组织的保护作用基础上,应用去唾液基EPO(asialoEPO)取代rhEPO对于鼠神经组织损伤实施保护。这种rhEPO的变异分子拥有很短的体内半衰期(1.4 min),且没有促进红细胞生成的作用,达到甚至优于广于rhEPO的组织保护作用。Leist[16]及其同事也合成了心得EPO的衍生物保留了组织保护作用,却没有促进红细胞增生的作用。这些对于临床应用EPO于组织保护方面又迈出了一大步。
【参考文献】
1 Masuda S.A novel site of erythropoietin production. Oxygen-dependent production in cultured rat astrocytes.J Biol Chem,1994,269(30):19488-19493.
2 Erbayraktar S.Erythropoietin is a multifunctional tissue-protective cytokine.Curr Hematol Rep,2003,2(6):465-470.
3 Juul S.Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage.Acta Paediatr,2002,91(438):36-42.
4 Bocker-Meffert S.Erythropoietin and VEGF promote neural outgrowth from retinal explants in postnatal rats.Invest Ophthalmol Vis Sci,2002,43(6):2021-2026.
5 Jaquet K.Erythropoietin and VEGF exhibit equal angiogenic potential.Microvasc Res,2002,64(2):326-333.
6 Ogilvie, M.Erythropoietin Stimulates Proliferation and Interferes with Differentiation of Myoblasts. J Biol Chem,2000, 275, 39754-39761.
7 Sakanaka M.In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A,1998,95(8):4635-4640.
8 Calvillo L.Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A,2003,100 (8): 4802-4806.
9 Moon C.Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A,2003,100(20):11612-11617.
10 Wright GL.Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. FASEB J, 2004 Jun;18(9):1031-1033. Epub 2004 Apr 1.
11 Cai Zheqing.Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation,2003,108(1):79-85. Epub 2003 Jun 09.
12 Tramontano AF.Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun,2003,308(4):990-994.
13 Cai Zheqing, Semenza GL.Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury.Circulation,2004,109(17):2050-2053.
14 Shi Y.Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. Basic Res Cardiol,99(3):173-182.
15 Erbayraktar s.Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci U S A,2003,100(11):6741-6746.
16 Leist M.Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science, 2004,305(5681):239-242.
- 上一篇:肝源性溃疡101例临床分析
- 下一篇:护理实验教学现状及改革