大鼠对急性胃内和静脉注射磷酸盐的肠道反应

Intestinal Response to Acute Intragastric and Intravenous Administration of Phosphate in Rats.

作者信息

Layunta Elena, Pastor Arroyo Eva Maria, Kägi Larissa, Thomas Linto, Levi Moshe, Hernando Nati, Wagner Carsten A

机构信息

Institute of Physiology, University of Zurich, Zurich, Switzerland.

Switzerland and National Center for Competence in Research NCCR Kidney.CH, University of Zurich, Zurich, Switzerland.

出版信息

Cell Physiol Biochem. 2019;52(4):838-849. doi: 10.33594/000000058.

DOI:10.33594/000000058

PMID:30946558

Abstract

BACKGROUND/AIMS: Phosphate (Pi) homeostasis is controlled by the intestine and kidneys whose capacities to transport Pi are under endocrine control. Several studies point to intestinal absorption as a therapeutic target to modulate Pi homeostasis. The small intestine is responsible for almost all Pi absorption in the gut, a process involving Na-dependent and independent mechanisms. Three Na-dependent Pi cotransporters have been described in the gastrointestinal tract: NaPi-IIb (a SLC34 member) and Pit-1 and Pit-2 (SLC20 transporters). We recently analysed the acute hormonal and renal response to intragastric (i.g) and intravenous (i.v) Pi-loading. This study demonstrated that the kidney quickly adapts to Pi-loading, with changes manifesting earlier in the i.v than i.g intervention. The aim of this work was to extend the previous studies in order to investigate the acute adaptation of intestinal transport of Pi and expression of intestinal Na/Pi-cotransporters in response to acute Pi-loading.

METHODS

Duodenal and jejunal mucosa was collected 40 minutes and/or 4 hours after administration (i.g and i.v) of either NaCl or Pi to anaesthetized rats. Uptakes of Pi and protein expression of Na/Pi cotransporters were measured in brush border membrane vesicles (BBMV); the cotransporters' mRNA abundance was quantified by real-time PCR in total RNA extracted from whole mucosa.

RESULTS

Pi-loading did not modify transport of Pi in duodenal and jejunal BBMV 4 hours after treatment. Administration of Pi did not alter either the intestinal expression of NaPi-IIb and Pit-2 mRNAs, whereas Pit-1 mRNA expression was only regulated (diminished) in duodenum collected 4 hours after i.g Pi-loading. NaPi-IIb protein expression was decreased in duodenum 4 hours upon i.v Pi infusion, whereas the duodenal and jejunal abundance of the cotransporter was unaffected by i.g administration of Pi.

CONCLUSION

Together, these data suggest that the intestine responds acutely to Pi-loading, though this response seems slower than the renal adaptation.

摘要

背景/目的：磷酸盐（Pi）稳态由肠道和肾脏控制，它们转运Pi的能力受内分泌控制。多项研究指出肠道吸收是调节Pi稳态的一个治疗靶点。小肠负责肠道内几乎所有的Pi吸收，这一过程涉及钠依赖和非依赖机制。胃肠道中已描述了三种钠依赖的Pi共转运体：NaPi-IIb（SLC34成员）以及Pit-1和Pit-2（SLC20转运体）。我们最近分析了胃内（i.g）和静脉内（i.v）Pi负荷后的急性激素和肾脏反应。这项研究表明，肾脏能迅速适应Pi负荷，静脉内干预比胃内干预的变化出现得更早。这项工作的目的是扩展先前的研究，以调查Pi急性负荷后肠道Pi转运的急性适应性以及肠道钠/磷共转运体的表达。

方法

在向麻醉大鼠经胃内（i.g）和静脉内（i.v）给予NaCl或Pi后40分钟和/或4小时收集十二指肠和空肠黏膜。在刷状缘膜囊泡（BBMV）中测量Pi摄取和钠/磷共转运体的蛋白表达；通过实时PCR对从全黏膜提取的总RNA中的共转运体mRNA丰度进行定量。

结果

Pi负荷在治疗后4小时未改变十二指肠和空肠BBMV中Pi的转运。给予Pi未改变NaPi-IIb和Pit-2 mRNA的肠道表达，而仅在胃内给予Pi后4小时收集的十二指肠中，Pit-1 mRNA表达受到调节（减少）。静脉内输注Pi后4小时，十二指肠中NaPi-IIb蛋白表达降低，而胃内给予Pi未影响十二指肠和空肠中共转运体的丰度。