Immunosuppressant
Effect of Rapamycin on Wound Healing: An Experimental Study

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Abstract

The aim of this study was to investigate the effects of rapamycin (RAPA) on the healing of bladder and abdominal wound closures. Fourteen male Sprague Dawley rats were randomized to receive either RAPA (3 mg/d) or placebo. A midline laparotomy was performed. The bladder was cut and closed with 4-0 Vicryl in a double layer. The fascia was closed with 0 nylon suture, and the skin closed with a subcuticular 2-0 nylon suture. The mean RAPA level was 9.1 ng/mg. Eosinophil and neutrophil infiltration, and the presence and degree of myofibroblast proliferation were significantly higher in the bladder, fascia, and dermis of the control group. Lymphocyte infiltration was similar in each group. Mean microvessel density as well as the percentage of cells expressing vascular endothelial growth factor in the bladder, fascia, and dermis were significantly lower among the RAPA group. Both proliferating cell nuclear antigen labeling indices for inflammatory cells in the fascia, dermal fibroblasts, and epithelial cells in the placebo group were significantly higher. No difference was observed for hydroxyproline levels in both the bladder and fascia between the groups. In conclusion, we found that RAPA treatment affected all steps of the wound healing process by decreasing the inflammatory cell number, angiogenesis, and myofibroblast proliferation, so the wound healing process was delayed and consequently the tensile strength of the wound decreased.

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Animals

Fourteen male Sprague Dawley rats were obtained from our Laboratory Animal Center. The animals were housed in separate cages in a temperature-controlled room with alternating 12-hour light–dark cycles, and acclimatized for at least 7 days before use. They were fed standard laboratory chow until the night before the operation, and were given water ad libitum. All experimental manipulations were undertaken in accordance with the National Institutes of Health Guide for the Care and Use of

Results

None of the animals in either group had a full-thickness wound dehiscence. Mean RAPA levels were 9.1 ± 0.8 ng/ml. Eosinophil infiltration was significantly higher in the bladder (P = .01), fascia (P = .004), and dermis (P = .01) of the control group. Neutrophil leukocyte infiltration also was significantly high in the bladder (P = .01), fascia (P = .02), and dermis (P = .02) in the control group. The lymphocyte infiltration was similar in each group.

The presence and degree of myofibroblast was

Discussion

RAPA is a potent new immunosuppressive agent that has been shown to significantly reduce the incidence of acute rejection. RAPA had other advantages; for example, unlike calcineurin inhibitors, it is not nephrotoxic and, by decreasing fibrosis, may prevent chronic rejection and stenosis at tracheal anastomoses. Unfortunately, RAPA inhibits the proliferation of fibroblasts; there are concerns that this effect may compromise the healing of certain tissues. Some studies have reported high wound

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