Pagel H, Fandrey J, Schobersberger W, Fuchs D, Jelkmann W
Institute of Physiology, Medical University, Lübeck, Germany.
Eur J Haematol. 1999 May;62(5):341-5. doi: 10.1111/j.1600-0609.1999.tb01913.x.
Activation of the human cellular immune system is associated with greatly increased formation of the pteridines neopterin and 7,8-dihydroneopterin. It has been postulated that pteridines play a role in the pathogenesis of the anaemia of inflammation. Herein, we studied effects of pteridines on renal function, primarily on the synthesis of erythropoietin (Epo). The experiments were performed with isolated rat kidneys which were perfused hypoxically (pO2 26 mmHg) at constant pressure (100 mmHg) in a serum-free recirculation system for 3 h. The results show that the rate of the production of Epo was significantly lowered when neopterin or 7,8-dihydroneopterin were added to the perfusate. Neopterin (200 microM) also reduced the renal Epo mRNA level. Both pteridines increased renal vascular resistance. 7,8-Dihydroneopterin lowered urine flow and glomerular filtration rate more potently than neopterin. Renal O2 consumption and parameters of exocrine renal function (fractional reabsorption rates of sodium, glucose and water) were not altered by the pteridines, while the glomerular permeability was greatly increased. These results suggest that activated macrophages may not only inhibit the synthesis of Epo by generating cytokines and reactive O2 species but also by the release of pteridines. In vivo, high concentrations of pteridines in renal tissue may aggravate the anaemia of inflammation.
人类细胞免疫系统的激活与蝶啶新蝶呤和7,8 - 二氢新蝶呤的生成大幅增加有关。据推测，蝶啶在炎症性贫血的发病机制中起作用。在此，我们研究了蝶啶对肾功能的影响，主要是对促红细胞生成素（Epo）合成的影响。实验使用分离的大鼠肾脏，在无血清再循环系统中于恒定压力（100 mmHg）下进行低氧灌注（pO2 26 mmHg）3小时。结果表明，当向灌注液中添加新蝶呤或7,8 - 二氢新蝶呤时，Epo的生成速率显著降低。新蝶呤（200 microM）也降低了肾脏Epo mRNA水平。两种蝶啶均增加了肾血管阻力。7,8 - 二氢新蝶呤比新蝶呤更有效地降低了尿流量和肾小球滤过率。蝶啶未改变肾脏耗氧量和外分泌肾功能参数（钠、葡萄糖和水的分数重吸收率），而肾小球通透性大大增加。这些结果表明，活化的巨噬细胞不仅可能通过产生细胞因子和活性氧来抑制Epo的合成，还可能通过释放蝶啶来抑制。在体内，肾组织中高浓度的蝶啶可能会加重炎症性贫血。
