Recombinant human growth hormone and glutamine synergistically improve the adaptation of the remnant small intestine in rats with short bowel syndrome

OBJECTIVE: To study the effects and the underlying mechanism of recombinant human growth hormone (rhGH) and glutamine (Gln) on the adaptation of the remnant small intestine in parenterally nourished, short bowel syndrome (SBS) rats. METHOD: Four parenteral nutrition (PN) treatment groups of SBS rats were randomly arranged in a 2 × 2 factorial design as follows: (i) STD (standard PN) group (–rhGH, –Gln); (ii) Gln group (–rhGH, +Gln); (iii) rhGH group (+rhGH, –Gln); and (iv) rhGH + Gln group (+rhGH, +Gln). Morphological changes of the intestinal mucosa were investigated and the expression of proliferating cell nuclear antigen (PCNA) and the occurrence of apoptosis were observed by immunohistochemical staining and terminal deoxynucleotidyl transfer-mediated dUTP-biotin nick end-labeling (TUNEL) methods. The level of intestinal insulin-like growth factor-1 (IGF-1) mRNA was determined by northern blotting. RESULTS: The mucosal thickness, villous height, crypt depth and villous surface area of the remnant small intestine in the rhGH + Gln group were increased significantly as compared with the other three experimental groups, and there were synergistic effects between rhGH and Gln (P < 0.01). The expression of PCNA was higher in the rhGH + Gln group than in the rhGH, Gln and STD groups (24.95 ± 3.93 vs 19.28 ± 3.25, 17.27 ± 3.38, and 8.37 ± 2.23 positive cells per crypt of Lieberkuhn, respectively; P < 0.01) but the rate of apoptosis was lower in the rhGH + Gln group than in the rhGH, Gln and STD groups (5.68 ± 2.07 vs 8.06 ± 2.33, 10.00 ± 2.24 and 22.32 ± 3.84 positive cells per 100 cells, respectively; P < 0.01). The intestinal IGF-1 mRNA was also expressed at a higher level in the rhGH + Gln group than in the rhGH, Gln and STD groups (0.73 ± 0.05 vs 0.62 ± 0.04 vs 0.51 ± 0.04 and 0.41 ± 0.22, respectively; P < 0.05). CONCLUSION: The synergistic combination of rhGH and Gln can significantly improve the adaptation of the remnant small intestine in parenterally fed SBS rats. An increase in cell proliferation and a decrease in cell apoptosis are both responsible for the intestinal adaptation. An increase in local IGF-1 plays an important role in this process.