Lacchini M L, Lopes A G, Malnic G, Giebisch G
Department of Physiology, Instituto de Ciencias Biomedicas, University Sao Paulo, Brasil.
Ren Physiol Biochem. 1992 Mar-Apr;15(2):106-12. doi: 10.1159/000173448.
Rats were given a 4- to 6-mg/kg body weight intraperitoneal injection of the antitumor drug, Cisplatin, 5-7 days prior to experiments to study tubule acidification by clearance and stationary microperfusion techniques. Cisplatin reduced the glomerular filtration rate markedly and caused a moderate degree of metabolic acidosis, but urine acidification (pH) was well maintained. Proximal tubule stationary pH and bicarbonate concentrations, as measured by pH microelectrodes, were significantly increased. The defect of proximal H+ secretion is reflected by increased acidification half-times (from 4.44 to 10.2 s) and reduced bicarbonate reabsorption to 37% of control values. H-ion back flux, measured during tubule and capillary perfusions with Ringer's bicarbonate- and CO2-free phosphate solutions, was reduced to 68% of control values. The apparent H-ion permeability was lowered from 0.79 to 0.54 cm/s. These results indicate that proximal acidification is reduced by impairment of H+ transport and not by increased transepithelial H+ shunting. Blunted acidification is compatible with a reduction in the number of Na/H exchangers in the proximal brush border and/or a decrease in the apical sodium gradient, the driving force for proximal H-ion secretion. Cortical distal tubule acidification, measured by double-barreled ion-exchange resin/PD microelectrodes, was not significantly affected by Cisplatin. This accounts for the observation that, in spite of the impaired proximal acidification, urine pH is kept within the normal range.
在实验前5 - 7天，给大鼠腹腔注射4 - 6毫克/千克体重的抗肿瘤药物顺铂，以通过清除率和固定微灌注技术研究肾小管酸化情况。顺铂显著降低了肾小球滤过率，并导致中度代谢性酸中毒，但尿液酸化（pH值）保持良好。用pH微电极测量的近端肾小管固定pH值和碳酸氢盐浓度显著升高。近端H⁺分泌缺陷表现为酸化半衰期延长（从4.44秒增至10.2秒），碳酸氢盐重吸收降至对照值的37%。在用无碳酸氢盐和二氧化碳的林格氏磷酸盐溶液进行肾小管和毛细血管灌注期间测量的H⁺反向通量降至对照值的68%。表观H⁺通透性从0.79厘米/秒降至0.54厘米/秒。这些结果表明，近端酸化是由于H⁺转运受损而非跨上皮H⁺分流增加所致。酸化减弱与近端刷状缘中Na⁺/H⁺交换体数量减少和/或顶端钠梯度降低（近端H⁺分泌的驱动力）相一致。用双管离子交换树脂/PD微电极测量的皮质远端肾小管酸化不受顺铂显著影响。这解释了尽管近端酸化受损，但尿液pH值仍保持在正常范围内这一现象。
