Gentamicin Nephrotoxicity in the Dog: Sequential Light and Electron Microscopy
Gentamicin Nephrotoxicity in the Dog: Sequential Light and Electron Microscopy
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庆大霉素对狗的肾毒性：连续光学和电子显微镜检查
DOI：
10.1177/030098588001700209
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发表时间：
1980
影响因子：
2.4
通讯作者：
G. Ishizaki
中科院分区：
文献类型：
--
作者：
W. Spangler;R. Adelman;G. Conzelman;G. Ishizaki
6只犬在用药前、用药后第5、9和12天，每8h肌肉注射庆大霉素10 mg/kg，连续行经皮肾活检。每日测定肾功能(血尿素氮、血肌酐)和尿酶排泄量(β葡萄糖醛酸酶、N-乙酰氨基葡萄糖苷酶、半乳糖苷酶和溶菌胺酶)。药物治疗前肾活检PAS染色3-μm切片显示近端肾小管上皮苍白肿胀，阻塞管腔。所有近端小管的顶面(刷缘)染色较深。第5天，刷状边缘染色减少或消失，近端小管胞浆内有许多开放的管腔和透明小球。超微结构显示胞浆内溶酶体数增多，多数含有较大的板层包涵体(髓鞘形态)。第9天的活检以细胞质透明小球的大小和数量增加为特征，没有刷状边缘染色。散在的近端小管细胞呈坏死状。完整的近端小管和肾单位的其他部分经常含有无定形颗粒管型或坏死性碎片。在超微结构上，近端小管具有完整的刷状边缘，所有类型的溶酶体的数量和大小均显著增加。在第12天，这些变化的严重程度加重，胞浆内有大量的胞质颗粒。尿酶(β葡萄糖醛酸酶和N-乙酰氨基葡萄糖苷酶)水平在第2天升高，半乳糖苷酶在第4天升高，溶菌胺酶在第5天升高。尿酶排泄量升高和肾小管形态严重改变是临床显著升高血肌酐(第6天)和血尿素氮(第12天)的先兆。
Sequential percutaneous renal biopsies in six dogs given gentamicin at 10 mg/kg every 8 hours (intramuscular) were examined before treatment and 5, 9 and 12 days after treatment. Renal function tests (blood urea nitrogen and serum creatinine) and urinary enzyme excretion (β glucuronidase, N acetyl-glucosaminidase, galactosidase and muramidase) were measured daily. Periodic acid Schiff (PAS)-stained, 3-μm sections of renal biopsies taken before drug treatment showed pale and swollen proximal tubular epithelium that occluded the tubular lumen. The apical surface of all proximal tubules (brush border) stained intensely. On day 5, brush border staining was decreased or absent and many proximal tubules had open lumina and hyaline globules in the cytoplasm. Ultrastructurally, the numbers of cytoplasmic lysosomes were increased and most contained large lamellar inclusions (myelin figures). Biopsies on day 9 were characterized by an increase in the size and number of cytoplasmic hyaline globules and an absence of brush border staining. Scattered proximal tubule cells were necrotic. Intact proximal tubules and other parts of the nephron frequently contained amorphous granular casts or necrotic debris. Ultrastructurally, proximal tubules had intact brush borders and showed a remarkable increase in the number and size of lysosomes of all types. On day 12 the severity of these changes progressed, and cytosegrosomes became numerous. Urinary enzyme levels (β glucuronidase and N acetyl-glucosaminidase) were elevated by day 2, galactosidase elevated by day 4 and muramidase elevated by day 5. Clinically significant elevations in serum creatinine (day 6) and blood urea nitrogen (day 12) were preceded by elevations in urinary enzyme excretion and by severe alterations in renal tubular morphology.