|
5总结
多种因子相互作用引起视网膜新生血管形成和BRB破坏，是目前研究表明的糖尿病视网膜病变的主要发病机制。在这个机制中起主要作用的因子为VEGF、IGF1、TNFα、IL1β、FGF等。各种研究表明EPO是新的独立的潜在的糖尿病视网膜病变的血管源性因子。而EPO在DR发病中所起的作用，在不同研究中有不同的表现。EPO/EPOR系统对神经系统的营养和神经保护作用已有明确的结论[40]，近年来的实验室研究同样表明EPO/EPOR系统参与了缺血的视网膜神经元的保护。腹腔注射EPO的糖尿病大鼠能够有效地抑制视网膜神经元的损坏。同时也有研究表明EPO/EPOR系统在增殖性糖尿病视网膜病变患者的视网膜新生血管的形成中起着重要的作用。阻断EPO可以抑制玻璃体的新生血管的形成。EPO在糖尿病视网膜病变治疗中的研究尚处于起步阶段，动物试验表明外生性EPO在在早期糖尿病大鼠的玻璃体内注射可防止视网膜细胞的死亡和保护RBR的功能，这可能是对早期DR治疗的一种新的方法。但对晚期的糖尿病视网膜病变的治疗是否可能引起视网膜新生血管的产生，有待进一步的研究。另外，长期大量使用EPO可能产生一些副作用有待进一步的解决。
【参考文献】
1朱鸿，施彩虹.血浆内皮素在糖尿病视网膜病变中诊断价值的ROC曲线分析.国际眼科杂志2005;5(5):10161019
2张小玲，邱曙东,陈艳炯,等.糖尿病性视网膜病变发病机制研究进展.国际眼科杂志 2005;5(6):12391241
3 Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol1994;118:445 450
4 Saishin Y, Takahashi K, Melia M, et al. Inhibition of Protein Kinase C Decreases ProstaglandinInduced Break down of the BloodRrtinal Barrier. J Cell Physiol2003;195(2):210219
5 Watanabe D. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. Nippon Ganka Gakkai Zasshi2007;111(11):892898
6 Recny MA, scooble HA, Kim Y. Structural characterization of natural human urinary and recombinant DNAderived erythropoietin.Identification of desarginine 166.erythropoietin. JBiol Chem1987;262(35):1715617163
7 Ratcliffe PJ, Jones RW, Phillips RE, et al. Oxygendependent modulation of erythropoietin mRNA levels in isolated rat kidneys studied by RNase protection. J Exp Med1990;172:657660
8 Ratcliffe PF, Schofield C. Oxygen sensing by HIF hydronylases. Nat Rev Mol Cell Biol2004;5:343354
9戴毅.红细胞生成素.国外临床生化与检验分册 2002;23(3):128132
10樊华，翟明.红细胞生成素受体和信号传递.日本医学介绍2000;21(3):137138
11 Mulcahy L. Thy erythropoirtin preceptor. Semin Oncol2001;28(2):1923
12 Miura Y, Miura O, Ihle JN, et al. Actication of the mitogen activated protein kinase pathway by the erythropoietin receptor. J Biol Chem1994;269:2996229969
13 GarcíaRamírez M, Hernndez C, Simó R. Expression of erythropoietin and its receptor in the human retina: a comparative study of diabetic and nondiabetic subjects. Diabetes Care2008;31(6):11891194
14刘鹏飞,惠延年,谢小萍.促红细胞生成素受体抑制小鼠视网膜新生血管形成.国际眼科杂志2008;8(3):507509
15 Patel S, Rowe MJ, Winters SA, et al. Elevated erythropoietin mRNA and protein concentrations in the developing human eye. Pediatr Res2008;63(4):394397
16 AsensioSnchez VM, GómezRamírez V, MoralesGómez I. Erythropoietin concentrations in the vitreous body from patients with proliferative diabetic retinopathy. Arch Soc Esp Oftalmol2008;83(3):169172
17朱弼珺，王卫峻,许讯,等. rhEPO对早期糖尿病大鼠视网膜超微结构和EPOR表达的信号的影响.眼科新进展 2007;27(8):581584
18 Jonas JB, Neumaier M. Erythropoietin levels in aqueous humour in eyes with exudative agerelated macular degeneration and diabetic retinopathy. Clin Experiment Ophthalmol2007;35(2):186187
19 Hernndez C, Fonollosa A, GarcíaRamírez M, et al. Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema. Diabetes Care2006;29(9):20282033
20 Brines ML, Ghezzi P, Keenan S, et al. Erytheropoietin crosses the bloodbrain barrier to protece against experimental brain injury. Proc Natl Acod Sci USA2000;97(19):1052610531
21 Grimm C, Wenzel A, Stanescu D, et al. Constitutive over expression of human erythropoietin protects the mouse retina against induced but not inherited retinal degeneration. J Neurosci2004;24(25):56515658
22 Bianchi R, Buynkakilli B, Brines M, et al. Erythropoietin both protects from and reverses experimental diabetic neuroptaty. Proc Natl Acad Sci USA2004;101(3):823 828
23 Villa P, Bigini P, Mennini T, et al. Erthropoirtin selectively attennates eytokine production and inflammation in celebral is chemia by targeting neuronal potosis. JEXP Med2003;198(6):971975
24 Ribatti D, Presta M, Vacca A, et al. Human erythropoirtin induces a proangiogenic phenotype in eultured dndothelial cells and stimulats neo vascularization in vivo. Blood1999;93(8)26272636
25 Digicaylioglu M, Liption SA. Erythropoietinmediated neuroprotection.involves crosstalk between Jakzand NFKB signaling cascades. Nature2001;412(6847): 641647
26 Luo L, Kaminoh Y, Chen HY, et al. Expression of erythropoietin and its receptor in normal and neovascularized murine corneas induced by alkali burns. Int J Ophthalmol(Guoji Yanke Zazhi)2008;8(5):857860
27俞梅，郭景和.子宫颈病变中促红细胞生成素受体表达及其与微血管密度的相关性研究.中国现代实用医学杂志2005;54:1 4
28 Kase S, Saito W, Ohgami K, et al. Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy. Br J Ophthalmol2007;91(10):13761378
29 Takagi H, Watanabe D, Suzuma K, et al. Novel role of erythropoietin in proliferative diabetic retinopathy. Diabetes Res Clin Pract2007;77(1):6264
30郭燕，王万辉.促红细胞生成素对急性高眼压大鼠视网膜的保护作用.国际眼科杂志2007;7(3):688691
31 Zhang J, Wu Y, Jin Y, et al. Intravitreal injection of erythropoietin protects both retinal vascular and neuronal cells in early diabetes. Invest Ophthalmol Vis Sci2008;49(2):732742
32 Morishita E, Masuda S, Nagao M, et al. Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamateinduced neuronal death. Neuroscience1997;76(1): 105116
33 Erbayraktar S, Grasso G, Sfacteria A, et al. Asialo erythropoietin is a nonery thropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci USA2003;100(11):67416746
34 Liu XZ, Xu XM, Hu R, et al. Neuronal and glial apotosis after traumatic spinal cord injury. J Neurosci1997;17(14):53955406
35 Bethea JR, Castro M, Keane RW, et al. Traumaticspinal cord injury induces nuclear factorkappaB activation. J Neurosci1998;18(9):32513260
36 Masuda S, Nagao M, Takahata K, et al. Functional erythropoietin receptor of the cells with neural characteristics. J Biol Chem1993;268(15):1120811216
37 Campana WM, Misasi R, O Brien JS, et al. Identification of a neurotrophic sequence in erythropoietin. Int J Mol Med1998;1(1):235241
38 Leist M, Chezzi P,Grasso G, et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science2004;305(9):239242
39 Digicaylioglu M, Garden GA, Timber blake S, et al. Acute neuroprotective synergy of erythropoietin and insulinlike groweh factor I. Proc Natl Acad Sci USA2004;101(26):98559860
40李丹,段宣初.促红细胞生成素对视神经视网膜的保护作用.国际眼科杂志2006;6(4):860864 上一页 [1] [2] |
