Lelievre-Pegorier M, Gilbert T, Sakly R, Meulemans A, Merlet-Benichou C
Antimicrob Agents Chemother. 1987 Jan;31(1):88-92. doi: 10.1128/AAC.31.1.88.
Clearance experiments were performed with young pups born of guinea pigs given a daily injection of 4 mg of gentamicin per kg (body weight) from days 48 to 54 of gestation (term, 68 days). For 3-day-old animals, the glomerular filtration rate was similar to that measured in control guinea pigs of the same age whose mothers were given saline during the same period of gestation. The same applied to fractional excretion of water, urea, total solutes, Na, K, Ca, and Mg but not to fractional phosphate excretion, which increased significantly in the gentamicin group when compared with the controls (mean +/- standard error, 21.7 +/- 4.9 versus 7.3 +/- 1.8%; P less than 0.05; n = 6 for both). The glomerular volume of the juxtamedullary nephrons diminished by about 40%, and their proximal tubule length decreased by about 20%. The glomerular volume of the superficial nephrons also diminished, by about 30%, but their proximal tubule length did not change. The gentamicin concentration was higher in the renal cortex than in the medulla (13.1 +/- 2.6 versus 5.7 +/- 2.2 micrograms/g [dry wt]; P less than 0.01; n = 6 for each). It decreased significantly from days 3 to 20 in both tissues. No functional impairment of the kidney was found in 10-day-old animals, and normal or even supranormal morphometry of the nephrons was observed in the 20-day-old animals. It is concluded that fetal exposure to gentamicin impairs proximal tubular function in the developing animal and might also adversely affect glomerular and tubular growth. However, both the functional and morphometric impairments of nephrons are transitory.
对豚鼠幼崽进行清除实验,这些豚鼠幼崽的母亲在妊娠第48至54天(妊娠期为68天)每天每千克(体重)注射4毫克庆大霉素。对于3日龄的动物,其肾小球滤过率与同龄对照豚鼠相似,对照豚鼠的母亲在相同妊娠期接受的是生理盐水注射。水、尿素、总溶质、钠、钾、钙和镁的排泄分数情况也是如此,但磷酸盐排泄分数不同,与对照组相比,庆大霉素组的磷酸盐排泄分数显著增加(平均值±标准误,分别为21.7±4.9与7.3±1.8%;P<0.05;两组均为n = 6)。近髓肾单位的肾小球体积减少了约40%,其近端小管长度减少了约20%。浅表肾单位的肾小球体积也减少了约30%,但其近端小管长度没有变化。肾皮质中的庆大霉素浓度高于髓质(分别为13.1±2.6与5.7±2.2微克/克[干重];P<0.01;每组n = 6)。在两种组织中,庆大霉素浓度从第3天到第20天均显著下降。在10日龄动物中未发现肾脏功能受损,在20日龄动物中观察到肾单位的形态测量正常甚至超常。结论是,胎儿期接触庆大霉素会损害发育中动物的近端小管功能,也可能对肾小球和肾小管的生长产生不利影响。然而,肾单位的功能和形态测量损伤都是暂时的。