Lane P H, Snelling D M, Hollman A, Langer W J
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198-2169, USA.
Pediatr Nephrol. 2001 Dec;16(12):1033-9. doi: 10.1007/s004670100020.
Prepubertal years of diabetes mellitus are relatively protected from clinical manifestations of nephropathy. Transforming growth factor-beta1 (TGF-beta1) is a major mediator of diabetic kidney disease. Its renal expression, translation, and activation change with sexual maturation in the normal rat. The role of TGF-beta1 in postpubertal susceptibility to diabetic renal hypertrophy was addressed in the present study. Male Sprague- Dawley rats were given streptozocin at 4 weeks of age (weanling) or 14 weeks of age (mature) and treated with insulin to maintain blood glucose levels between 300 and 500 mg/dl. Nondiabetic controls received saline. After 6 weeks with ad libitum food and water, kidneys were snap-frozen for measurement of TGF-beta1 protein and mRNA. As in previous studies, diabetic renal hypertrophy was blunted in weanling animals compared with mature rats. Message for TGF-beta1 was not significantly increased in weanling animals [102 (9)% [mean (SEM)] in nondiabetic controls versus 117 (10)% in diabetic rats; P=0.91], while it was significantly increased in mature diabetic animals [100 (7)% vs. 146 (11)%; P=0.01]. Immunohistochemistry revealed focal increases in glomerular staining in mature but not weanling diabetic rats. Differences in the control of the renal TGF-beta system may explain the permissive role of puberty in the manifestations of diabetic kidney disease.
青春期前的糖尿病患者相对不易出现肾病的临床表现。转化生长因子-β1（TGF-β1）是糖尿病肾病的主要介质。在正常大鼠中，其在肾脏的表达、翻译和激活会随着性成熟而发生变化。本研究探讨了TGF-β1在青春期后对糖尿病性肾肥大易感性中的作用。雄性Sprague-Dawley大鼠在4周龄（断奶期）或14周龄（成熟期）时接受链脲佐菌素处理，并用胰岛素治疗以维持血糖水平在300至500mg/dl之间。非糖尿病对照组接受生理盐水。在随意进食和饮水6周后，将肾脏速冻以测量TGF-β1蛋白和mRNA。与之前的研究一样，与成熟大鼠相比，断奶期动物的糖尿病性肾肥大不明显。断奶期动物中TGF-β1的信使RNA没有显著增加[非糖尿病对照组为102（9）%[平均值（标准误）]，糖尿病大鼠为117（10）%；P = 0.91]，而在成熟的糖尿病动物中显著增加[100（7）%对146（11）%；P = 0.01]。免疫组织化学显示，成熟的糖尿病大鼠肾小球染色有局灶性增加，而断奶期糖尿病大鼠则没有。肾脏TGF-β系统调控的差异可能解释了青春期在糖尿病肾病表现中的促进作用。
