Garland H O, Phipps D J, Harpur E S
Department of Physiological Sciences, University of Manchester, U.K.
J Pharmacol Exp Ther. 1992 Oct;263(1):293-7.
Two independent techniques were used in anesthetized rats in an attempt to locate the nephron site of the reduced tubular calcium reabsorption accompanying acute gentamicin infusion. The first technique was that of lithium clearance used to assess proximal sodium (and secondarily calcium) handling. Observations that lithium clearance was comparable in control and gentamicin-treated animals (1.83 +/- 0.39 vs. 1.46 +/- 0.14 ml.min-1 for first experimental period) suggests a lack of proximal effect of the drug. The second technique was that of tracer microinjection whereby superficial nephrons were injected with 45Ca and tubule calcium transport was assessed from the recovery of radioactivity in the final urine. 45Ca recovery values from distal microinjections were comparable in control and gentamicin-treated groups (81.1 +/- 2.0 vs. 77.7 +/- 4.6%). However, 45Ca recovery values from proximal microinjections were significantly higher in the gentamicin group (9.4 +/- 1.0 vs. 3.5 +/- 0.8%; P < .001). These data suggest that the effects of gentamicin on renal calcium handling are mediated at a nephron site proximal to the distal tubule (i.e., loop of Henle or proximal tubule itself). Closer examination of individual proximal micropuncture data may point to an effect occurring predominantly in the pars recta of the proximal tubule or loop of Henle. Taken together, the results of both parts of the present study suggest that the early physiological effects of gentamicin on the kidney occur in a different nephron segment from any subsequent nephrotoxicity.
在麻醉大鼠中使用了两种独立技术，试图确定急性输注庆大霉素时肾小管钙重吸收减少的肾单位部位。第一种技术是利用锂清除率来评估近端钠（以及继发性钙）的处理情况。观察发现，对照组和庆大霉素处理组的锂清除率相当（第一个实验期分别为1.83±0.39和1.46±0.14 ml·min⁻¹），这表明该药物对近端无影响。第二种技术是微量注射示踪剂，向浅表肾单位注射⁴⁵Ca，并根据最终尿液中放射性的回收率评估肾小管钙转运。对照组和庆大霉素处理组远端微量注射的⁴⁵Ca回收率相当（分别为81.1±2.0%和77.7±4.6%）。然而，庆大霉素组近端微量注射的⁴⁵Ca回收率显著更高（分别为9.4±1.0%和3.5±0.8%；P<0.001）。这些数据表明，庆大霉素对肾钙处理的影响是在远曲小管近端的肾单位部位（即髓袢或近端小管本身）介导的。对个体近端微穿刺数据的进一步检查可能会指出主要发生在近端小管直部或髓袢的影响。综上所述，本研究两部分的结果表明，庆大霉素对肾脏的早期生理作用发生在与任何后续肾毒性不同的肾单位节段。
