Transport of gentamicin in rat proximal tubule.
Transport of gentamicin in rat proximal tubule.
复制标题
庆大霉素在大鼠近曲小管中的转运。
DOI：
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
H. Sobel
中科院分区：
文献类型：
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作者：
R. Wedeen;Batuman;C. Cheeks;E. Marquet;H. Sobel
通过组合免疫荧光和切片冷冻干燥放射自显影技术确定氚庆大霉素（GM）在大鼠体内的肾内分布，这些技术允许在扩散再分布之前和之后进行亚细胞定位。还通过电子显微镜检查了这些肾脏的组织。胃肠外给予 4 至 100 mg/kg 后，GM 在近曲小管的 S1 和 S2 段积聚，但不在 S3 段积聚。 10 分钟内，放射自显影显示近端和远端肾小管腔内存在 3H-GM；在许多近端细胞中，与胞饮摄取一致的亚顶端分布是显着的。 1小时后，在冷冻干燥放射自显影切片中，3H-GM广泛分布在细胞质内，细胞内隔离的证据极少。此时，3H-GM 可能位于内吞液泡内，电子显微镜仅显示出含有单髓体的罕见液泡。随后，切片冷冻干燥放射自显影显示氨基糖苷的隔离，但在注射后长达 6 小时的荧光显微镜组织处理过程中，这种细胞内定位丢失。 6小时时，含有多个组织良好的髓鞘质的大细胞质空泡首先出现在S1和S2节段中。到 48 小时，3H-GM 牢固地结合在这些空泡中，并在冷冻干燥放射自显影切片和免疫荧光制剂中保持在原位，并与电子显微镜下含有多髓体的空泡数量增加相关。因此，这些研究证明了细胞内可扩散的 3H-Gm 可在给药后 1 至 6 小时引发肾毒性。
The intrarenal distribution of tritiated gentamicin (GM) was determined in rat by combined immunofluorescence and section freeze-dry autoradiography, techniques that permit subcellular localization before and after diffusional redistribution. Tissue from these kidneys was also examined by electron microscopy. After parenteral administration of 4 to 100 mg/kg, GM accumulates in S1 and S2 but not S3 segments of proximal tubules. Within 10 minutes, autoradiography demonstrates 3H-GM in the lumina of proximal and distal tubules; a subapical distribution consistent with pinocytotic uptake is prominent in many proximal cells. After 1 hour, 3H-GM is diffusely distributed within the cytoplasm in section freeze-dry autoradiographs with minimal evidence of intracellular sequestration. At this time, 3H-GM is presumably within endocytotic vacuoles, and electron microscopy reveals only rare vacuoles containing single myeloid bodies. Subsequently, section freeze-dry autoradiography shows sequestration of the aminoglycoside, but this intracellular localization is lost during tissue processing for fluorescent microscopy up to 6 hours after injection. At 6 hours large cytoplasmic vacuoles containing multiple well-organized myelin figures first appear in S1 and S2 segments. By 48 hours, 3H-GM is firmly bound in these vacuoles and is maintained in situ in both section freeze-dry autoradiographs and immunofluorescent preparations in association with increased numbers of vacuoles containing multiple myeloid bodies by electron microscopy. These studies thus demonstrate diffusible 3H-Gm within the cell which is available to initiate nephrotoxicity 1 to 6 hours after administration.