Epidermal growth factor improves intestinal adaptation during somatostatin administration in vivo.
Somatostatin (SMS) is administered to patients with short bowel syndrome and enterocutaneous fistulae. Previous studies have shown detrimental effects of SMS on intestinal adaptation after bowel resection. We examined whether administration of epidermal growth factor (EGF) could reverse the deleterious effects of SMS seen after enterectomy. Sixty-four Sprague-Dawley rats underwent an 80% small bowel resection or transection as control. Rats received either SMS at 50 ng x kg(-1) x h(-1), EGF/Urogastrone at 1.5 microg x kg(1-) x h(-1), or both via subcutaneous miniosmotic pumps. Samples were obtained at 1 day and 1 week after surgery for histologic examination, analysis of apical Na+/glucose cotransporter protein and mRNA expression, and analysis of basolateral Na+/K+ ATPase protein and mRNA expression. Protein expression was analyzed by Western blotting whereas mRNA expression was compared by ribonuclease protection assay. Histologically, villus to crypt length after intestinal resection showed increased adaptation in EGF/SMS vs SMS treated animals in both jejunum and ileum. Analysis of mRNA and protein of epithelial transporters show early increases when EGF is administered with SMS vs SMS only. We conclude that combination therapy using EGF and SMS may be beneficial to intestinal adaptation after small bowel resection. Both histologic and molecular data suggest an enhanced absorptive potential and adaptation of the remaining intestine when EGF is administered.
Liu
C D
CD
Department of Surgery, UCLA Medical Center, Los Angeles 90024, USA.
Rongione
A J
AJ
Shin
M S
MS
Ashley
S W
SW
McFadden
D W
DW
D000704:Analysis of Variance; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*
D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D013004:Somatostatin; D004815:Epidermal Growth Factor; D000254:Sodium-Potassium-Exchanging ATPase