INSULIN-LIKE GROWTH-FACTOR-I PREVENTS GUT ATROPHY AND MAINTAINS INTESTINAL INTEGRITY IN SEPTIC RATS

Background: The effects of insulin-like growth factor-I (IGF-I) on gut metabolism, structure, and barrier function as well as its general anabolic effects were investigated in septic rats. Methods: Thirty-three male Wistar rats that underwent cecal ligation were randomly divided into one of the following two groups: (1) received only total parenteral nutrition(control group) or (2) received total parenteral nutrition with IGF-I (IGF group) at a dose of 4 mg/kg/d for 3 days. Results: During the 3-day period, the body weight of rats in the IGF group increased significantly over that of rats in the control group (17.1 +/- 2.6 vs 5.8 +/- 4.6 g, p < .01). The total and free IGF-I plasma concentrations were significantly higher in the IGF group than in the control group. The cumulative nitrogen balance was significantly more positive for the IGF group (423.9 +/- 24.3 mg of nitrogen) than for the control group (290.8 +/- 26.0 mg of nitrogen). The weights of thymus, spleen, and kidneys were significantly increased in the IGF group compared with weights in the control group. Treatment with IGF-I improved the gut mucosal weight in all regions of the gut examined, including duodenum, jejunum, ileum, and colon. Histologic and biochemical analyses of the jejunum showed greater villus height and crypt depth and higher mucosal DNA and protein content in the IGF group. The arterial concentration of endotoxin was not significantly different between the two groups, whereas its level in portal blood was significantly lower in the IGF group (23.2 +/- 9.9 pg/mL) than in the control group (95.5 +/- 37.9 pg/mL), an indication that IGF-I treatment decreased the amount of endotoxin that traversed the gut barrier. Conclusions: These results indicate that IGF-I can improve gut metabolism and reduce mucosal atrophy and that it may play a role in maintaining the gut barrier function in sepsis.