McAuliffe A V, Brooks B A, Fisher E J, Molyneaux L M, Yue D K
Department of Life Sciences in Nursing, University of Sydney, Sydney, Australia.
Nephron. 1998 Nov;80(3):277-84. doi: 10.1159/000045187.
The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA1c, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon's signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.
抗坏血酸（AA）作为一种抗氧化剂的重要作用在糖尿病中尤为相关，糖尿病患者血浆中AA浓度会降低。本研究旨在评估用AA或醛糖还原酶抑制剂托瑞司他进行治疗对糖尿病患者AA代谢和尿白蛋白排泄的影响。从20名糖尿病受试者中在0、3、6、9和12个月时采集血液和尿液样本，这些受试者被随机分为两组，分别接受每日两次口服500毫克AA或安慰剂。在所有时间点测量收缩压和舒张压、糖化血红蛋白、血脂、尿白蛋白和总糖胺聚糖排泄，在0和12个月时测量硫酸乙酰肝素（糖胺聚糖）。对于16名每天接受200毫克托瑞司他治疗的糖尿病受试者，在0和3个月时测定相同参数以及尿AA排泄。AA治疗可使血浆AA升高（方差分析，F值 = 12.1，p = 0.004），并在9个月后降低白蛋白排泄率（AER）（方差分析，F值 = 3.2，p = 0.03），但未改变所测量的其他参数。托瑞司他降低了血浆AA（威尔科克森符号秩检验，p < 0.05），但未改变AER或所测量的其他参数。AA治疗降低AER的能力可能与细胞外基质的变化或氧化防御机制的改善有关。与糖尿病大鼠模型不同，醛糖还原酶的抑制并未使人类血浆AA或AER恢复正常。事实上，托瑞司他降低了血浆AA浓度，这一现象可能是由于AA利用增加所致。糖尿病患者通过饮食补充AA可能对减轻糖尿病并发症的进展具有长期益处。
