Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, PO Box 100275, 1600 SW Archer Rd, Gainesville, FL, 32610, USA.
Urolithiasis. 2019 Jun;47(3):243-254. doi: 10.1007/s00240-018-1067-5. Epub 2018 Jun 14.
In rats, we recently showed how a chronic metabolic acidosis simultaneously reduced urinary oxalate excretion and promoted oxalate secretion by the distal colon leading to the proposition that acid-base disturbances may trigger changes to renal and intestinal oxalate handling. The present study sought to reproduce and extend these observations using the mouse model, where the availability of targeted gene knockouts (KOs) would offer future opportunities to reveal some of the underlying transporters and mechanisms involved. Mice were provided with a sustained load of acid (NHCl), base (NaHCO) or the carbonic anhydrase inhibitor acetazolamide (ATZ) for 7 days after which time the impacts on urinary oxalate excretion and its transport by the intestine were evaluated. Mice consuming NHCl developed a metabolic acidosis but urinary oxalate was only reduced 46% and not statistically different from the control group, while provision of NaHCO provoked a significant 2.6-fold increase in oxalate excretion. For mice receiving ATZ, the rate of urinary oxalate excretion did not change significantly. Critically, none of these treatments altered the fluxes of oxalate (or chloride) across the distal ileum, cecum or distal colon. Hence, we were unable to produce the same effects of a metabolic acidosis in mice that we had previously found in rats, failing to find any evidence of the 'gut-kidney axis' influencing oxalate handling in response to various acid-base challenges. Despite the potential advantages offered by KO mice, this model species is not suitable for exploring how acid-base status regulates oxalate handling between the kidney and intestine.
在大鼠中，我们最近研究了慢性代谢性酸中毒如何同时降低尿草酸盐排泄并促进远端结肠的草酸盐分泌，从而提出酸碱性紊乱可能会导致肾脏和肠道草酸盐处理发生变化。本研究旨在使用小鼠模型重现和扩展这些观察结果，其中靶向基因敲除（KO）的可用性将为未来揭示涉及的一些潜在转运体和机制提供机会。在 7 天的时间里，向小鼠提供持续的酸（NHCl）、碱（NaHCO）或碳酸酐酶抑制剂乙酰唑胺（ATZ）负荷，然后评估其对尿草酸盐排泄及其在肠道中的转运的影响。摄入 NHCl 的小鼠发生代谢性酸中毒，但尿草酸盐仅减少 46%，与对照组无统计学差异，而提供 NaHCO 则引起草酸盐排泄显著增加 2.6 倍。对于接受 ATZ 的小鼠，尿草酸盐排泄率没有明显变化。关键的是，这些处理都没有改变草酸盐（或氯离子）在回肠、盲肠或远端结肠的通量。因此，我们无法在小鼠中产生与我们之前在大鼠中发现的代谢性酸中毒相同的效果，未能找到任何证据表明“肠-肾轴”影响各种酸碱挑战下的草酸盐处理。尽管 KO 小鼠具有潜在的优势，但这种模型物种不适合探索酸碱状态如何调节肾脏和肠道之间的草酸盐处理。
