|Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
As suture ties usually drop out from the mucosa, matrix metalloprotcinases [MMPs] are induced in the gastrointestinal tract more than the skin. We investigated the role of MMPs in wound healing by using BE16627B, a MMP inhibitor and tacrolimus (FK506), an immune suppressant.
The identical surgical procedure, colon anastomosis (single-layer, inverted) and implantation of an osmotic pumps (model 1003, Alza, Palo Alto, CA) in the left side of the back, was performed in seventy-six Sprague Dawley rats, 270-290g BW. The animals were randomly assigned to receive 10mg of BE16627B, tacrolimus, at a dose of 0.01, 0.1, or 1.0mg/kg/day, or the solution only in the osmotic pump. Animals were sacrificed 4 days after surgery, and colon-bursting pressure (mm Hg) and hydroxyproline (μg/mg wet tissue, index of collagen) were measured.
BE16627B significantly increased colon bursting pressure (160±12 vs 125±7, p<0.05) and the soluble fraction of collagen (0.27±.01 vs 0.21±.01, p<0.01) in the anastomosis. Tacrolimus significantly increased colon-bursting pressure (146±9, 158±10, 151±6; 0.01, 0.1 and 1.0mg/kg/day, respectively) more than the control (119±7, p<0.01). Collagenase activity of the control was less than the 0.01 mg/kg/day (p<0.05), although collagenase activities were decreased dose dependently by tacrolimus (p<0.05).
These findings demonstrate that inhibition of MMP activity increases wound strength and deposition of the soluble fraction of collagen. The data demonstrate that tacrolimus during acute anastomotic healing enhances wound strength even though decreased collagen concentration. Farther investigation of wound healing mechanism is needed in both collagen synthesis and collagenolysis.