Kennedy A, Frank R N, Varma S D
Invest Ophthalmol Vis Sci. 1983 Sep;24(9):1250-8.
Isolated microvessels (primarily capillaries) from bovine retina and cerebral cortex, as well as cultured bovine retinal capillary pericytes and porcine and canine retinal capillary endothelial cells contain apparent aldose reductase activity. This conclusion is based on the ability of these cultured cells and vessel fragments to reduce DL-glyceraldehyde in preference to D-glucuronate at low (0.1 mM) substrate concentrations, in the presence of NADPH, and in the accumulation of high levels of sorbitol or galactitol when retinal pericytes and endothelial cells are cultured in media enriched in glucose or galactose. The quantitative similarities of these activities in bovine retinal and cerebral microvessels, as well as the quantitatively similar ability of these two sets of microvessels to oxidize 14C-labeled glucose with the label either in the C-1 or the C-6 position, suggests that aldose reductase may not be a major causal factor in diabetic retinopathy. This conclusion is suggested because, while these metabolic activities are similar in bovine retinal and cerebral microvessels, only the retinal microvasculature suffers major anatomic and functional damage in diabetes. This conclusion must be viewed with caution, however, because other metabolic pathways that we have not investigated may be altered by an excess of sugar alcohols, and be present in differing activities in retinal and cerebral microvessels; species differences may exist; and similar experiments have not been conducted using human microvessels.
来自牛视网膜和大脑皮层的分离微血管(主要是毛细血管),以及培养的牛视网膜毛细血管周细胞和猪及犬视网膜毛细血管内皮细胞含有明显的醛糖还原酶活性。这一结论基于这些培养细胞和血管片段在低(0.1 mM)底物浓度下、存在NADPH时优先还原DL-甘油醛而非D-葡萄糖醛酸的能力,以及当视网膜周细胞和内皮细胞在富含葡萄糖或半乳糖的培养基中培养时,山梨醇或半乳糖醇的高水平积累。牛视网膜和大脑微血管中这些活性的定量相似性,以及这两组微血管氧化C-1或C-6位置带有14C标记的葡萄糖的定量相似能力,表明醛糖还原酶可能不是糖尿病视网膜病变的主要致病因素。提出这一结论是因为,虽然这些代谢活性在牛视网膜和大脑微血管中相似,但只有视网膜微血管在糖尿病中遭受主要的解剖和功能损伤。然而,必须谨慎看待这一结论,因为我们尚未研究的其他代谢途径可能会因过量的糖醇而改变,并且在视网膜和大脑微血管中的活性不同;可能存在物种差异;并且尚未使用人类微血管进行类似实验。