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精氨酸-谷氨酰胺在幼鼠早产儿视网膜病变模型中的应用

http://www.cnophol.com 2009-4-14 16:27:52 中华眼科在线

  DISCUSSION

  Many studies indicate that one of the proposed mechanisms for the pathogenesis of ROP includes overproduction of the angiogenic growth factors including VEGF[6,7], resulting invasoconstriction, poor blood flow, and ultimately retinal ischemia. Nutritional factors may play a major role in regulation of these mechanisms. Recent studies of retinal pigment epithelial cells in culture have demonstrated that glutamine deprivation results in a dramatic elevation of VEGF[8].In studies of mammary epithelium, glutamine deprivation increased both VEGF and IL8, a potent neutrophil chemoattractant, and these same changes were evident with arginine deprivation[9].In addition, several studies in animals suggest that glutamine supplementation reduces inflammation[10,11]. Premature infants undergoing intensive care are also frequently deprived of both arginine and glutamine[12,13] because of stress. They are unable to maintain endogenous synthesis of these conditionally essential amino acids, making these infants highly vulnerable to glutamine andarginine deprivation. Glutamine and arginine supplementation have both been shown to be safe in lowbirthweight infants[14,15].Recent studies indicated that arginine and glutamine (ArgGln) can improve blood flow to the microvasculature via increased local nitric oxide production through the Largininenitric oxide synthase pathway[16,17]. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study is to demonstrate the beneficial effects of a nutraceutic agent, ArgGln dipeptide, in inhibiting retinal angiogenesis. The proposed mechanism is a reduction of VEGF expression in vivo. It may provide a safe way to prevent and treat some forms of proliferative retinopathies including ROP.

   【参考文献】

   1 Wang P, Tao LJ, Gao XR, Xie LH, Yang HL, Wang XL, Xiong S, Xiao ZG, Guo Y, Tang XR, Yang JF, Qi ZY. Clinical analysis of retinopathy of prematurity. Int J Ophthalmol(Guoji Yanke Zazhi)2007;7(6):17131715

  2 Filho JB F , Barros CK, Eckert GU , Procianoy L, Procianoy RS. Retinopathy of prematurity in a tertiary center in south of Brazil. Int J Ophthalmol(Guoji Yanke Zazhi)2007;7(1):3135

  3 Li SG, Zeng J. New development of retinopathy of prematurity. Int J
Ophthalmol(Guoji Yanke Zazhi) 2006;6(5):11171119

  4 Smith LE, Wesolowski E, McLellan A, Kostyk SK, DAmato R, Sullivan R, DAmore PA. Oxygeninduced retinopathy in the mouse. Invest Ophthalmol Vis Sci1994;35:101111

  5 Lutty GA, McLeod DS. A new technique for visualization of the human retinal vasculature. Arch Ophthalmol 1992;110:267276

  6 Smith LE. Pathogenesis of retinopathy of prematurity. Growth Horm IGF Res2004;14(Suppl A):S140144

  7 Zhang Q, Wei H. Recent advances in retinopathy of prematurity. Int JOphthalmol(Guoji Yanke Zazhi)2007;7(5):14031405

  8 Abcouwer SF, Marjon PL, Loper RK, Vander Jagt DL. Response of VEGF expression to amino acid deprivation and inducers of endoplasmic reticulum stress. Invest Ophthalmol Vis Sci2002;43:27912798

  9 Marjon PL, BobrovnikovaMarjon EV, Abcouwer SF. Expression of the proangiogenic factors vascular endothelial growth factor and interleukin8/CXCL8 by human breast carcinomas is responsive to nutrient deprivation and endoplasmic reticulum stress. Mol Cancer2004;3:4

  10 Li N, Liboni K, Fang MZ, Samuelson D, Lewis P, Patel R, Neu J. Glutamine decreases lipopolysaccharideinduced intestinal inflammation in infant rats. Am J Physiol Gastrointest Liver Physiol2004;286:G914921

  11 Liboni K, Li N, Neu J. Mechanism of glutaminemediated amelioration of lipopolysaccharideinduced IL8 production in Caco2 cells. Cytokine2004;26:5765

  12 Neu J. Glutamine supplements in premature infants: why and how. J Pediatr Gastroenterol Nutr2003;37:533535

  13 Wu G, Jaeger LA, Bazer FW, Rhoads JM. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. JNutr Biochem2004;15:442451

  14 Poindexter BB, Ehrenkranz RA, Stoll BJ, Wright LL, Poole WK, Oh W, Bauer CR, Papile LA, Tyson JE, Carlo WA, Laptook AR, Narendran V, Stevenson DK, Fanaroff AA, Korones SB, Shankaran S, Finer NN, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network. Parenteral glutamine supplementation does not reduce the risk of mortality or lateonset sepsis in extremely low birth weight infants. Pediatrics2004;113:12091215

  15 Vaughn P, Thomas P, Clark R, Neu J. Enteral glutamine supplementation and morbidity in low birth weight infants. J Pediatr2003;142:662668

  16 Amin HJ, Zamora SA, McMillan DD, Fick GH, Butzner JD, Parsons HG, Scott RB. Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr2002;140:425431

  17 Zhao Y, Ren B, Gao XW. Current research in mechanism and drug therapy of retinopathy of prematurity. Int J Ophthalmol(Guoji Yanke Zazhi)2006;6(6):13821385

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