title: 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.
authors.affiliation: Department of Surgery, Zhongshan Hospital, Shanghai, 200032, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: Z H
authors.initials: ZH
authors.lastname: Wu
authors.forename: J X
authors.initials: JX
authors.lastname: Xie
authors.forename: D Y
authors.initials: DY
authors.lastname: Jin
authors.forename: H C
authors.initials: HC
authors.lastname: Zhuo
mesh_terms: D000220:Adaptation, Biological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D019587:Dietary Supplements; D004357:Drug Synergism; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology*; D007422:Intestines / Q000601:surgery; D008297:Male; D010288:Parenteral Nutrition; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000378:metabolism / Q000628:therapy*
chemical_list: D012333:RNA, Messenger; D005973:Glutamine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone