Kowluru R A, Engerman R L, Kern T S
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison 53706-1532, USA.
Free Radic Biol Med. 1999 Feb;26(3-4):371-8. doi: 10.1016/s0891-5849(98)00210-x.
Metabolic abnormalities observed in retina and in cerebral cortex were compared in diabetic rats and experimentally galactosemic rats. Diabetes or experimental galactosemia of 2 months duration significantly increased oxidative stress in retina, as shown by elevation of retinal thiobarbituric acid reactive substances (TBARS) and subnormal activities of antioxidant defense enzymes, but had no such effect in the cerebral cortex. Activities of sodium potassium adenosine triphosphatase [(Na,K)-ATPase] and calcium ATPase became subnormal in retina as well as in cerebral cortex. In contrast, protein kinase C (PKC) activity was elevated in retina but not in cerebral cortex in the same hyperglycemic rats. Dietary supplementation with an antioxidant mixture (containing ascorbic acid, Trolox, alpha-tocopherol acetate, N-acetyl cysteine, beta-carotene, and selenium) prevented the diabetes-induced and galactosemia-induced elevation of retinal oxidative stress, the elevation of retinal PKC activity and the decrease of retinal ATPases. In cerebral cortex, administration of the antioxidant diet also prevented the diabetes-induced decreases in (Na,K)-ATPase and calcium ATPases, but had no effect on TBARS and activities of PKC and antioxidant-defense enzymes. The results indicate that retina and cerebral cortex differ distinctly in their response to elevation of tissue hexose, and that cerebral cortex is more resistant than retina to diabetes-induced oxidative stress. The greater resistance to oxidative stress in cerebral cortex, as compared to retina, is consistent with the resistance of cerebral cortex to microvascular disease in diabetes, and with a hypothesis that oxidative stress contributes to microvascular disease in diabetes. Dietary supplementation with these antioxidants offers a means to inhibit multiple hyperglycemia-induced retinal metabolic abnormalities.
在糖尿病大鼠和实验性半乳糖血症大鼠中，比较了视网膜和大脑皮质中观察到的代谢异常。持续2个月的糖尿病或实验性半乳糖血症显著增加了视网膜中的氧化应激，表现为视网膜硫代巴比妥酸反应性物质（TBARS）升高以及抗氧化防御酶活性低于正常水平，但在大脑皮质中没有这种作用。视网膜和大脑皮质中钠钾腺苷三磷酸酶[（Na，K）-ATP酶]和钙ATP酶的活性均低于正常水平。相反，在相同的高血糖大鼠中，视网膜中的蛋白激酶C（PKC）活性升高，而大脑皮质中则没有。用抗氧化剂混合物（含有抗坏血酸、曲克芦丁、α-生育酚醋酸酯、N-乙酰半胱氨酸、β-胡萝卜素和硒）进行饮食补充，可预防糖尿病诱导和半乳糖血症诱导的视网膜氧化应激升高、视网膜PKC活性升高以及视网膜ATP酶降低。在大脑皮质中，给予抗氧化剂饮食也可预防糖尿病诱导的（Na，K）-ATP酶和钙ATP酶降低，但对TBARS以及PKC和抗氧化防御酶的活性没有影响。结果表明，视网膜和大脑皮质对组织己糖升高的反应明显不同，并且大脑皮质比视网膜对糖尿病诱导的氧化应激更具抵抗力。与视网膜相比，大脑皮质对氧化应激的抵抗力更强，这与大脑皮质对糖尿病微血管疾病的抵抗力以及氧化应激导致糖尿病微血管疾病的假说一致。用这些抗氧化剂进行饮食补充提供了一种抑制多种高血糖诱导的视网膜代谢异常的方法。
