Abstract
It is well recognized that ileostomy patients suffer from chronic depletion of Na+ through the stoma effluent. In this study we evaluated the effects of ileostomy on messenger RNA levels that encode different Na+/H+ exchanger isoforms (NHE-2 and NHE-3). Loop ileostomies were created in Sprague-Dawley rats. Segments of diverted ileum were harvested for quantitation of mRNA levels encoding these isoforms and the Na+/K+ ATPase in mucosal scrapings and for immunofluorescence microscopy, specifically of the NHE-3 protein. Our studies indicate that as early as 8 days after diversion, NHE-3 gene expression is selectively attenuated in poststomal ileal mucosa. Mucosal morphology remains undisturbed, and the distribution of protein expression along the crypt/villus axis is not altered. Infusion of Na+ or the enterocyte nutrient, glutamine, into the lumen of the diverted segment restores or even augments mRNA levels for NHE-3, again without altering the histologic appearance or distribution of the protein along the crypt/ villus axis. These effects are specific because nonpolar osmolytes (mannitol) and related organic nutrients not specific for the enterocyte (i.e., butyrate) have no effect on mRNA levels of NHE-3. Further work is required to understand how the early changes in mRNA contribute to mucosal function and response to luminal diversion.
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Supported by grant RO1 DK 44571-11 from the National Institutes of Health and by funds from the Brigham Surgical Group Foundation.
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Doble, M.A., Tola, V.B., Chamberlain, S.A. et al. Luminal regulation of Na+/H+ exchanger gene expression in rat ileal mucosa. J Gastrointest Surg 6, 387–395 (2002). https://doi.org/10.1016/S1091-255X(01)00049-X
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DOI: https://doi.org/10.1016/S1091-255X(01)00049-X