The effect of insulin-like growth factor I on healing of colonic anastomoses in cortisone-treated rats

Abstract

Purpose: This study was designed to investigate whether intraperitoneally injected insulin-like growth factor I is able to protect colonic healing from the adverse effects of hydrocortisone therapy.

Methods: Eighty female Wistar rats were randomized into four groups (20 rats each). After resection of a segment of transverse colon, an end-to-end anastomosis was performed. Hydrocortisone (5 mg/kg body weight) was injected intramuscularly in rats of cortisone (Group B) and insulin-like growth factor I + cortisone (Group D) groups once daily for seven days before and after the operation. Insulin-like growth factor I (2 mg/kg body weight) was intraperitoneally injected in rats of the insulin-like growth factor I (Group C) and the insulin-like growth factor I + Cortisone (Group D) groups immediately after operation and on the second, fourth, and sixth postoperative days. Rats were killed on the seventh postoperative day. Anastomoses were graded macroscopically and histologically, and bursting pressures and anastomotic hydroxyproline levels were recorded. Statistical analyses were performed by using Fisher's exact test for the comparison of proportions and ANOVA for the comparison of means among groups with subsequent post-hoc analysis using Bonferroni correction.

Results: Leakage rate was significantly higher in the cortisone (Group B) group. Bursting pressures were significantly lower in the cortisone group, whereas they were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups (Group C and D). Histology revealed a significant decrease of inflammatory cell infiltration, neoangiogenesis, and fibroblast activity in the cortisone group compared with the control group, whereas these parameters were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups. Hydroxyproline levels were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups.

Conclusions: Hydrocortisone inhibits the healing of colonic anastomoses. However, insulin-like growth factor I given intraperitoneally mediates the deleterious effects of cortisone and protects colonic healing in rats.