Berndt Theresa, Thomas Leslie F, Craig Theodore A, Sommer Stacy, Li Xujian, Bergstralh Eric J, Kumar Rajiv
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11085-90. doi: 10.1073/pnas.0704446104. Epub 2007 Jun 12.
The mechanisms by which phosphorus homeostasis is preserved in mammals are not completely understood. We demonstrate the presence of a mechanism by which the intestine detects the presence of increased dietary phosphate and rapidly increases renal phosphate excretion. The mechanism is of physiological relevance because it maintains plasma phosphate concentrations in the normal range after ingestion of a phosphate-containing meal. When inorganic phosphate is infused into the duodenum, there is a rapid increase in the renal fractional excretion of phosphate (FE Pi). The phosphaturic effect of intestinal phosphate is specific for phosphate because administration of sodium chloride does not elicit a similar response. Phosphaturia after intestinal phosphate administration occurs in thyro-parathyroidectomized rats, demonstrating that parathyroid hormone is not essential for this effect. The increase in renal FE Pi in response to the intestinal administration of phosphate occurs without changes in plasma concentrations of phosphate (filtered load), parathyroid hormone, FGF-23, or secreted frizzled related protein-4. Denervation of the kidney does not attenuate phosphaturia elicited after intestinal phosphate administration. Phosphaturia is not elicited when phosphate is instilled in other parts of the gastrointestinal tract such as the stomach. Infusion of homogenates of the duodenal mucosa increases FE Pi, which demonstrates the presence of one or more substances within the intestinal mucosa that directly modulate renal phosphate reabsorption. Our experiments demonstrate the presence of a previously unrecognized phosphate gut-renal axis that rapidly modulates renal phosphate excretion after the intestinal administration of phosphate.
哺乳动物体内维持磷稳态的机制尚未完全明确。我们证实存在一种机制，即肠道能够检测到饮食中磷酸盐增加，并迅速增加肾脏对磷酸盐的排泄。该机制具有生理相关性，因为在摄入含磷餐后，它能将血浆磷酸盐浓度维持在正常范围内。当向十二指肠注入无机磷酸盐时，肾脏磷酸盐排泄分数（FE Pi）会迅速增加。肠道磷酸盐的促尿磷排泄作用对磷酸盐具有特异性，因为给予氯化钠不会引发类似反应。肠道给予磷酸盐后出现的尿磷增多现象在甲状腺-甲状旁腺切除的大鼠中也会发生，这表明甲状旁腺激素对该作用并非必不可少。肠道给予磷酸盐后，肾脏FE Pi增加，但血浆磷酸盐浓度（滤过负荷）、甲状旁腺激素、成纤维细胞生长因子23（FGF - 23）或分泌型卷曲相关蛋白4均无变化。肾脏去神经支配并不会减弱肠道给予磷酸盐后引发的尿磷增多现象。当磷酸盐注入胃肠道的其他部位（如胃）时，不会引发尿磷增多。注入十二指肠黏膜匀浆会增加FE Pi，这表明肠道黏膜内存在一种或多种直接调节肾脏磷酸盐重吸收的物质。我们的实验证实存在一种先前未被认识的磷酸盐肠-肾轴，在肠道给予磷酸盐后，该轴能迅速调节肾脏磷酸盐排泄。
