Georgescu A, Popov D
Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, 8 B.P.Hasdeu Street, 79691 Romania.
J Am Aging Assoc. 2000 Jan;23(1):33-40. doi: 10.1007/s11357-000-0005-x.
In this study we have investigated the occurrence of "classical" Amadori rearrangement products of AGE-proteins in the vascular mesenteric bed and in the lens of Golden Syrian hamsters (12 weeks old) rendered simultaneous hyperlipidemics-diabetics (HD), or hyperlipidemics (H) for 24 weeks. For the next 4 weeks the hamsters in HD and H groups received by gavage a solution of 3 mM L-arginine, with the intent to look for the potential effects of L-arginine on the fluorescence of tissular AGE-proteins. Age-matched normal hamsters were used as controls (C). The AGE-products of proteins, and the AGE-collagen isolated from the mesenteric bed were quantitated by fluorescence spectroscopy at ex: 370 nm/em: 440 nm. The results showed that: (i) compared to the fluorescence levels of AGE-proteins detected at C goup, in HD group the fluorescence of AGE-proteins was found 2.78 and 7.41 fold increased in the vascular mesenteric bed and lens, respectively; (ii) in H group the fluorescence of AGE-proteins was 2.36 fold augumented in the vascular mesenteric bed, and 5.43 fold in the lens (versus the C goup); (iii) the aging occurring during the 24 weeks of the experiment induced a small increase in AGE-proteins fluorescence in both mesentery (1.76 fold) and lens (3.83 fold), compared to the levels measured in C group at the inception of the study (12 weeks old hamsters); (iv) the fluorescence of AGE-proteins in the vascular mesenteric bed and in the lens of hamsters in HD and H groups correlated with the increase in circulating plasma glucose and cholesterol concentrations throughout the experiment; (v) L-arginine dietary supplementation in HD and H groups, diminished the AGE-collagen fluorescence in the mesentery to ∼ 35% and ∼ 17%, respectively; in the lens the fluorescence of AGE-proteins was reduced to 65-70% of the levels found in HD and H groups (at 24 weeks). This study showed for the first time that simultaneous hyperlipidemia-hyperglycemia induced an enhanced accumulation of fluorescent AGE-proteins in the mesentery and lens (comparatively to the effect of hyperlipidemia and of chronological aging monitored during the experiment), and that in vivo L-arginine administration decreased the fluorescence of tissular AGE-proteins (AGE-collagen included). The latter observation may bring another area of potential intervention in the adjunct efforts to find out inhibitors of AGE formation, and thus to reduce the increased levels of AGE-proteins accumulated in tissues when diabetes is additionally complicated with atherosclerosis.
在本研究中，我们调查了在同时患有高脂血症和糖尿病（HD）或单纯高脂血症（H）24周的12周龄金黄叙利亚仓鼠的血管系膜床和晶状体中，晚期糖基化终产物（AGE）-蛋白质的“经典”Amadori重排产物的发生情况。在接下来的4周里，HD组和H组的仓鼠通过灌胃给予3 mM L-精氨酸溶液，旨在探究L-精氨酸对组织中AGE-蛋白质荧光的潜在影响。年龄匹配的正常仓鼠用作对照（C）。通过荧光光谱法在激发波长为370 nm/发射波长为440 nm下对从系膜床分离的蛋白质AGE产物和AGE胶原蛋白进行定量。结果表明：（i）与C组检测到的AGE-蛋白质荧光水平相比，在HD组中，血管系膜床和晶状体中AGE-蛋白质的荧光分别增加了2.78倍和7.41倍；（ii）在H组中，血管系膜床中AGE-蛋白质的荧光增加了2.36倍，晶状体中增加了5.43倍（相对于C组）；（iii）与研究开始时（12周龄仓鼠）C组测量的水平相比，实验24周期间发生的衰老导致系膜（1.76倍）和晶状体（3.83倍）中AGE-蛋白质荧光略有增加；（iv）在整个实验过程中，HD组和H组仓鼠的血管系膜床和晶状体中AGE-蛋白质的荧光与循环血浆葡萄糖和胆固醇浓度的增加相关；（v）HD组和H组补充L-精氨酸饮食后，系膜中AGE-胶原蛋白的荧光分别降至约35%和17%；在晶状体中，AGE-蛋白质的荧光降至HD组和H组（24周时）所发现水平的65 - 70%。本研究首次表明，同时存在的高脂血症和高血糖症会导致系膜和晶状体中荧光性AGE-蛋白质的积累增加（与实验期间监测的高脂血症和自然衰老的影响相比），并且体内给予L-精氨酸可降低组织中AGE-蛋白质（包括AGE-胶原蛋白）的荧光。后一观察结果可能为寻找AGE形成抑制剂的辅助努力带来另一个潜在的干预领域，从而降低糖尿病合并动脉粥样硬化时组织中积累的AGE-蛋白质的增加水平。
