Effects of growth hormone (rhGH) and glutamine supplemented parenteral nutrition on intestinal adaptation in short bowel rats

Abstract

This study was performed to compare the effects of recombinant human growth hormone (rhGH), glutamine (Gln) and simultaneous treatment with rhGH and Gln in rats subjected to 75% intestinal resection and maintained with parenteral nutrition (PN) for 6 days. Morphological changes including mucosal thickness, villus height, crypt depths and villus surface area of the residue jejunum were measured under a light microscope; expression of PCNA as an index of cell proliferation and apoptotic cells were observed using immunohistochemical staining; Ileal IGF-1 mRNA was determined by Northern blot analysis. The morphological parameters of the jejunal mucosa in rats treated with PN alone were only about 52–62% of those in reference group (P<0.01), this atrophy of the jejunal mucosa was accompanied by a 2.5-fold decrease in absolute counts of PCNA and a 10-fold increase in apoptotic index (P<0.01), IGF-1 mRNA transcript in residue ileum was decreased significantly (P<0.01). However, with rhGH or Gln, the mucosal architecture was improved significantly and was further improved when rhGH and Gln were given together, the morphological values in rats treated with Gln+rhGH was 79% higher than those with PN alone, and was associated with a 2-fold increase in PCNA counts and a 4-fold decrease in apoptotic index (P<0.01), IGF-1 mRNA expression was 78% higher than those with PN alone (P<0.01). We conclude that rhGH and Gln have synergistic effects on adaptation of the intestinal remnant in parenterally fed, short-bowel rats. The underlying mechanisms are associated with increased proliferation and decreased apoptosis in the intestinal epithelial cells. Local intestinal production of IGF-1 plays an important role in adaptation of the small intestine. Our findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance the intestinal adaptation.