Insulin-like Growth Factor Administration Stimulates Wound Healing on Colonic Anastomosis in Hypoxic Rat Model

Objective: Intestinal anastomosis is among the most commonly performed major abdominal procedures; however, leaks are an ongoing problem. The aim of this study was to investigate the effect of Insulin-like Growth Factor (IGF-1) on colonic healing under hypoxia. Methods: Thirty-two Sprague–Dawley male rats underwent laparotomy with colonic transection and anastomosis. Rats were divided into four groups—Group A: normoxic (FiO2 21%) with saline [2 mg/kg, Intraperitoneally (IP)] at days 0, 2, 4, and 6; Group B: hypoxic (FiO2 11%) with saline injection; Group C: normoxic with IGF-1 injection at a dose of 2 mg/kg at days 0, 2, 4, and 6; Group D: hypoxic with IGF-1 treatment. On day 7, all animals were sacrificed, and intestine weight and bursting pressure were measured; anastomotic tissues were analyzed for mRNA level of collagen I and Matrix Metalloproteinase-13 (MMP-13) and cytokines analysis by enzyme-linked immunosorbent assay. Results: There was significant increase in intestinal length in normoxic group treated with IGF-1 as compared to control (129.9 cm vs. 99.38 cm, p < 0.05); the length increased significantly in hypoxic group treated with IGF as compared to hypoxic control (123.1 cm vs. 82.25, p < 0.01). In the normoxic groups, a 6.7% decrease in mean body weight was found; however, the normoxic IGF-1 group sustained a weight gain of 0.5% (p < 0.01). The average weight decreased in the hypoxic control group (28.3%) and in the hypoxic IGF-1 treated group (16.6%, p < 0.05). Anastomotic bursting pressure increased significantly (p < 0.05) after IGF-1 treatment. Collagen I and MMP-13 mRNA expressions increased significantly (p < 0.001) in the IGF-1 treated group. Interleukin-10 and tumor necrosis factor alpha levels decreased under hypoxia with IGF-1 (p < 0.05). Vascular endothelial growth factor (p < 0.001), transforming growth factor beta (p < 0.05), and IGF-1 (p < 0.001) were significantly elevated in response to IGF-1. Conclusion: IGF-1 stimulates the healing of colonic anastomosis under hypoxia. Factors promoting neoangiogenesis, collagen deposition, and paracrine expression were increased after IGF-1 treatment resulting in wound healing.