Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan A A, Rao P S, Sturman J A, Boles T H
Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
Am J Physiol. 1995 Sep;269(3 Pt 2):F429-38. doi: 10.1152/ajprenal.1995.269.3.F429.
We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.
我们研究了两种内源性抗氧化剂——牛磺酸和维生素E对实验性糖尿病大鼠肾功能的影响。用链脲佐菌素（STZ）诱导雄性Sprague-Dawley大鼠患糖尿病，将其分为以下几组：1）未治疗组；2）胰岛素治疗组，每天皮下注射6 U超长效胰岛素，分两次给药；3）牛磺酸补充组，饮用水中添加1%牛磺酸；4）维生素E补充组，饲料中添加100 IU维生素E/kg。动物饲养52周。除维生素E治疗组外，其他各组的存活率相似（70-90%），维生素E治疗组在6个月时84%的动物死亡。在52周时，与正常或胰岛素治疗的糖尿病大鼠相比，未治疗和牛磺酸治疗的STZ大鼠的肾小球滤过率升高。补充牛磺酸可使总蛋白尿和白蛋白尿减少近50%。这种治疗还可防止肾小球肥大，保留肾小球IV型胶原的免疫组化染色，并减少糖尿病动物的肾小球硬化和肾小管间质纤维化。牛磺酸治疗的糖尿病大鼠肾功能和结构的变化与肾皮质丙二醛含量正常化、血清游离Fe2+浓度降低以及皮肤胶原中晚期糖氧化产物戊糖苷和荧光形成减少有关。给予富含维生素E的饮食会加重STZ糖尿病大鼠的肾病。此外，补充维生素E会增加血清游离Fe2+浓度，增强肾脂质过氧化，并加速皮肤胶原中晚期糖基化终产物（AGEs）的积累。我们得出结论，给STZ糖尿病大鼠服用牛磺酸而非维生素E可改善糖尿病肾病。牛磺酸的有益作用与减少肾氧化损伤、降低脂质过氧化以及减少肾内AGEs的积累有关。
