Gilbert T, Lelievre-Pegorier M, Merlet-Benichou C
Unité de Recherches sur le Développement Normal et Pathologique des Fonctions Epithéliales, INSERM U 319, Université Paris 7, France.
Pediatr Res. 1991 Nov;30(5):450-6. doi: 10.1203/00006450-199111000-00011.
Renal clearance studies and morphologic observations were performed in rats aged 14, 21, and 28 d and 3, 6, 9, and 12 mo born with a 20% reduction in nephron number after administration of 75 mg/kg/d of gentamicin to their mothers during the second half of gestation. Gentamicin was still present in urine 3 mo after birth. Morphologic damage characteristic of gentamicin accumulation was observed in the kidney on d 14 and 21. Adequate compensatory adaptation to oligonephronia occurred for glomerular function within 14 d of birth, but tubular phosphate reabsorption was significantly low on d 21. On d 28, no evidence of histologic or functional damage to the kidney was observed. At 3 mo, mesangial lesions were observed in rats of the gentamicin group, whereas they were rarely present in 6-mo-old control rats. Furthermore, glomerular sclerotic lesions were already evident in about 5% of the juxtamedullary nephrons. The same percentage of injured nephrons was not observed before 12 mo in controls. Complementary morphologic data obtained in 24-mo-old rats showed that glomerulosclerosis involved 40% of the juxtamedullary nephron population at this age in animals of the gentamicin group versus 21% in controls. It is concluded that in the young rats born with oligonephronia of gentamicin-treated mothers neither the gentamicin remaining in the kidney cells nor the injuries it caused them prevented compensatory adaptation of the kidney to a reduced number of nephrons. However, although this oligonephronia was mild, it might have been sufficient to cause early development of glomerular sclerosis in the adults.
对妊娠后半期给予75mg/kg/d庆大霉素的母鼠所生的14日龄、21日龄、28日龄以及3月龄、6月龄、9月龄和12月龄大鼠进行了肾脏清除率研究和形态学观察。出生后3个月，尿液中仍可检测到庆大霉素。在第14天和第21天，观察到肾脏出现庆大霉素蓄积的特征性形态学损伤。出生后14天内，肾脏对肾小球功能进行了充分的代偿性适应，但在第21天，肾小管对磷酸盐的重吸收显著降低。在第28天，未观察到肾脏有组织学或功能损伤的证据。在3月龄时，庆大霉素组大鼠出现系膜病变，而在6月龄对照大鼠中很少见。此外，约5%的近髓肾单位已出现肾小球硬化病变。在对照组中，12月龄前未观察到相同比例的受损肾单位。对24月龄大鼠的补充形态学数据显示，庆大霉素组动物在这个年龄时，40%的近髓肾单位出现肾小球硬化，而对照组为21%。研究得出结论，在庆大霉素处理的母鼠所生的幼鼠中，无论是残留在肾细胞中的庆大霉素，还是其对肾细胞造成的损伤，都没有阻止肾脏对肾单位数量减少的代偿性适应。然而，尽管这种肾单位减少程度较轻，但可能足以导致成年期肾小球硬化的早期发展。
