Navegantes Luiz Carlos Carvalho, Mendes Glória Elisa Florido, Lira Eduardo Carvalho, Kettelhut Isis do Carmo, Baptista Maria Alice Sperto Ferreira, Burdmann Emmanuel A
Laboratory of Endocrinology and Metabolism, Department of Molecular Biology, São José do Rio Preto Medical School, São Paulo, Brazil.
Am J Nephrol. 2006;26(2):163-9. doi: 10.1159/000092983. Epub 2006 Apr 25.
To standardize microdialysis in rat kidneys and address cyclosporine A (CsA) effects on renal cortex and medulla interstitial glucose.
Munich-Wistar rats were treated with vehicle or CsA (15 mg/kg/day) for 3 weeks. Glucose was assessed by spectrophotometry in dialysate samples from cortex, medulla and arterial plasma. Plasma insulin was measured by radioimmunoassay. Renal blood flow (RBF) was measured by Doppler ultrasound. Creatinine and urea were measured by spectrophotometry.
CsA significantly increased the plasma levels of urea and creatinine (1.5 +/- 0.20 vs. 0.73 +/- 0.03 mg/dl in controls, p < 0.05). Medullary glucose in control was 44% lower than arterial glucose (56 +/- 6 vs. 101 +/- 8 mg/dl, p < 0.05). At the same time, CsA increased arterial (163 +/- 35 vs. 101 +/- 8 mg/dl in controls, p < 0.05) and medullary interstitial glucose (100 +/- 18 vs. 56 +/- 6 mg/dl in controls, p < 0.05), but did not affect cortical glucose (114 +/- 21 vs. 90 +/- 11 mg/dl in controls). These changes occurred in the presence of a decreased plasma insulin level (2.7 +/- 0.2 vs. 9.3 +/- 0.4 microU/ml in controls, p < 0.05). The increment in medullary glucose in CsA group occurred despite a reduction in RBF (4.6 +/- 0.8 vs. 6.5 +/- 1.0 ml/min/kidney in controls, p < 0.05).
Microdialysis was an adequate tool to investigate in vivo regulation of renal glucose metabolism. Renal glucose uptake was dependent on medullary cells and CsA treatment induced diabetogenic effects on renal medulla in situ.
规范大鼠肾脏微透析技术，并探讨环孢素A（CsA）对肾皮质和髓质间质葡萄糖的影响。
将慕尼黑-威斯塔大鼠用溶剂或CsA（15毫克/千克/天）处理3周。通过分光光度法评估来自皮质、髓质和动脉血浆的透析液样本中的葡萄糖。通过放射免疫分析法测量血浆胰岛素。通过多普勒超声测量肾血流量（RBF）。通过分光光度法测量肌酐和尿素。
CsA显著增加了血浆尿素和肌酐水平（对照组为1.5±0.20对0.73±0.03毫克/分升，p<0.05）。对照组髓质葡萄糖比动脉葡萄糖低44%（56±6对101±8毫克/分升，p<0.05）。同时，CsA增加了动脉（对照组为163±35对101±8毫克/分升，p<0.05）和髓质间质葡萄糖（对照组为100±18对56±6毫克/分升，p<0.05），但不影响皮质葡萄糖（对照组为114±21对90±11毫克/分升）。这些变化发生在血浆胰岛素水平降低的情况下（对照组为2.7±0.2对9.3±0.4微单位/毫升，p<0.05）。尽管RBF降低（对照组为4.6±0.8对6.5±1.0毫升/分钟/肾脏，p<0.05），CsA组髓质葡萄糖仍增加。
微透析是研究肾脏葡萄糖代谢体内调节的合适工具。肾脏葡萄糖摄取依赖于髓质细胞，CsA治疗对原位肾髓质产生致糖尿病作用。
