Yaqoob M, McClelland P, Patrick A W, Stevenson A, Mason H, White M C, Bell G M
Royal Liverpool University Hospital, UK.
QJM. 1994 Oct;87(10):601-7.
Two groups of patients with insulin-dependent diabetes mellitus of > 10 years duration and either persistent normoalbuminuria (group 1, n = 49; albumin excretion < 30 mg/day) or microalbuminuria (group 2, n = 33; albumin excretion 30-300 mg/day) were investigated for evidence of free oxygen radical activity (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl-glucosaminidase and leucine aminopeptidase) were also measured. Healthy controls (n = 38) were matched for age and sex. Groups 1 and 2 were similar in terms of age, sex, duration of diabetes and recent glycaemic control. Serum cholesterol and creatinine were similar in all three groups. Free-radical activity and oxidant injury were significantly higher in groups 1 and 2 than in controls (p < 0.001). Glomerular proteinuria, tubular proteinuria and enzymuria were significantly higher in group 2 than in group 1 and controls (p < 0.01). Group 1 had significantly higher transferrinuria, tubular enzymuria and tubular proteinuria than controls. However, groups 1 and 2 were similar in degree of free oxygen radical generation and oxidant injury. In diabetic nephropathy, oxidant injury and renal tubular damage accompany and may even precede microalbuminuria. The presence of these abnormalities in the absence of glomerular proteinuria favours the hypothesis that alterations first occur in the peritubular microcirculation, which by causing oxidant injury and tubular damage, may initiate diabetic nephropathy.
对两组病程超过10年的胰岛素依赖型糖尿病患者进行了研究。一组为持续正常白蛋白尿组（第1组，n = 49；白蛋白排泄量<30毫克/天），另一组为微量白蛋白尿组（第2组，n = 33；白蛋白排泄量30 - 300毫克/天），检测其自由基活性（红细胞超氧化物歧化酶和谷胱甘肽过氧化物酶）及氧化损伤（血清丙二醛）证据。还测定了肾小球蛋白尿（白蛋白尿、转铁蛋白尿）、肾小管蛋白尿（视黄醇结合蛋白）和肾小管酶尿（N - 乙酰 - 葡萄糖苷酶和亮氨酸氨肽酶）。选取年龄和性别相匹配的健康对照者（n = 38）。第1组和第2组在年龄、性别、糖尿病病程及近期血糖控制方面相似。三组的血清胆固醇和肌酐水平相近。第1组和第2组的自由基活性及氧化损伤显著高于对照组（p < 0.001）。第2组的肾小球蛋白尿、肾小管蛋白尿和酶尿显著高于第1组和对照组（p < 0.01）。第1组的转铁蛋白尿、肾小管酶尿和肾小管蛋白尿显著高于对照组。然而，第1组和第2组在自由基生成程度和氧化损伤方面相似。在糖尿病肾病中，氧化损伤和肾小管损伤伴随微量白蛋白尿出现，甚至可能先于微量白蛋白尿。在无肾小球蛋白尿的情况下出现这些异常情况，支持了以下假说：改变首先发生在肾小管周围微循环，通过引起氧化损伤和肾小管损伤，可能引发糖尿病肾病。
