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管腔渗透压下调大鼠结肠黏膜中钠/氢交换体(NHE3)的基因表达。

Luminal osmolarity downregulates gene expression of Na+/H+ exchanger (NHE3) in rat colon mucosa.

作者信息

Doble M A, Tola V B, Cima R R, Zinner M J, Klein M A, Soybel D I

机构信息

Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

出版信息

J Gastrointest Surg. 2000 Sep-Oct;4(5):531-5. doi: 10.1016/s1091-255x(00)80097-9.

DOI:10.1016/s1091-255x(00)80097-9
PMID:11077330
Abstract

Water-coupled Na&sup+ absorption in the colon is mediated principally by Na+/H+ exchange (isoforms NHE2 and NHE3). To determine whether luminal ion composition or osmolarity influences NHE expression in colon mucosa, two groups (n = 6 in each) of adult male Sprague-Dawley rats underwent sham laparotomy or loop ileostomy. In these studies, diversion did not markedly alter mRNA levels for NHE2, NHE3, or Na+/K+, at 8 or 21 days, indicating that loss of luminal volume does not alter NHE gene expression. To evaluate the effects of specific luminal components, we infused equal volumes of half-normal (154 mOsm) or iso-osmolar (308 mOsm) solutions of saline and mannitol into the diverted colon. All solutions elicited significant (45% to 60%; P <0.05) decreases in mRNA levels for NHE3, with iso-osmolar mannitol eliciting the greatest changes. Decreases in NHE2 and Na+/K+ mRNA levels were observed following these infusions but were not as marked as the changes for NHE3. These findings suggest that (1) loss of luminal Na+ is not, in itself, a signal that regulates NHE expression and (2) infusion of any solute, including Na+ itself, provides a signal to downregulate expression of NHE3 in colon mucosa.

摘要

结肠中与水偶联的钠离子吸收主要由钠/氢交换体(同工型NHE2和NHE3)介导。为了确定肠腔离子组成或渗透压是否影响结肠黏膜中NHE的表达,两组成年雄性Sprague-Dawley大鼠(每组n = 6)分别接受假剖腹手术或回肠造口术。在这些研究中,在第8天或第21天,肠腔改道并未显著改变NHE2、NHE3或钠/钾离子的mRNA水平,这表明肠腔容量的减少不会改变NHE基因的表达。为了评估特定肠腔成分的影响,我们向改道的结肠中注入等体积的半正常(154 mOsm)或等渗(308 mOsm)的生理盐水和甘露醇溶液。所有溶液均引起NHE3的mRNA水平显著下降(45%至60%;P <0.05),等渗甘露醇引起的变化最大。在这些注入后观察到NHE2和钠/钾离子mRNA水平下降,但不如NHE3的变化明显。这些发现表明:(1)肠腔钠离子的丢失本身并不是调节NHE表达的信号;(2)注入任何溶质,包括钠离子本身,都会提供一个信号来下调结肠黏膜中NHE3的表达。

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本文引用的文献

1
Selective decreases in levels of mRNA encoding a water channel (AQP3) in ileal mucosa after ileostomy in the rat.大鼠回肠造口术后回肠黏膜中编码水通道(AQP3)的mRNA水平选择性降低。
J Gastrointest Surg. 1999 Jan-Feb;3(1):54-60. doi: 10.1016/s1091-255x(99)80009-2.
2
Differential regulation of NHE isoforms by sodium depletion in proximal and distal segments of rat colon.大鼠结肠近端和远端节段中钠耗竭对NHE亚型的差异调节
Am J Physiol. 1999 Feb;276(2):G539-49. doi: 10.1152/ajpgi.1999.276.2.G539.
3
Molecular cloning and functional expression of a rat Na+/H+ exchanger (NHE5) highly expressed in brain.
在脑中高表达的大鼠钠氢交换体(NHE5)的分子克隆及功能表达
J Biol Chem. 1999 Feb 12;274(7):4383-8. doi: 10.1074/jbc.274.7.4383.
4
Immunochemical characterization of Na+/H+ exchanger isoform NHE4.钠离子/氢离子交换体亚型NHE4的免疫化学特性分析
Am J Physiol. 1998 Oct;275(4):F510-7. doi: 10.1152/ajprenal.1998.275.4.F510.
5
Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger.缺乏NHE3钠氢交换体的小鼠的肾脏和肠道吸收缺陷
Nat Genet. 1998 Jul;19(3):282-5. doi: 10.1038/969.
6
Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon.醛固酮通过增加大鼠近端结肠的NHE3表达来刺激肠道对钠的吸收。
Am J Physiol. 1998 Mar;274(3):C586-94. doi: 10.1152/ajpcell.1998.274.3.C586.
7
The Na+/H+ exchange isoform NHE3 regulates basal canine ileal Na+ absorption in vivo.钠/氢交换异构体NHE3在体内调节犬回肠的基础钠吸收。
Gastroenterology. 1997 Jan;112(1):174-83. doi: 10.1016/s0016-5085(97)70232-4.
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Am J Physiol. 1996 Jan;270(1 Pt 1):G29-41. doi: 10.1152/ajpgi.1996.270.1.G29.
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