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2002 Fiscal Year Final Research Report Summary

Study for expression and function of matrix metalloproteinase on wound healing

Research Project

Project/Area Number 13671260
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNippon Medical School

Principal Investigator

KIYAMA Teruo  Nippon Medical School, Department of Surgery (I), Lecturer, 医学部, 助手 (30246954)

Project Period (FY) 2001 – 2002
Keywordswound healing / matrix metalloproteinases / immune suppressant / gastrointestinal tract / collagen / FK506 / matrix metalloproteinase inhibitor / BE16627B
Research Abstract

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.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Witte MB, Kiyama T et al.: "Nitric oxide enhances experimental wound healing in diabetes"British Journal of Surgery. 36・4. 1594-1601 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teruo Kiyama et al.: "Tacrolimus enhances colon anastomotic healign in rats"Wound Repair and Regeneration. 10・5. 308-313 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teruo Kiyama et al.: "Effect of matrix metalloproteinase Inhibition on colonic anastomotic healing in rats"Journal of Gastrointestinal Surgery. 5・3. 303-311 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木山輝郎ほか: "ラット外傷モデルにおける栄養投与経路の検討"外科と代謝・栄養. 36・4. 185-190 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木山輝郎ほか: "免疫抑制剤Tacrolimusの術後代謝に及ぼす影響"日本消化器外科学会雑誌. 35・9. 1597 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木山輝郎ほか: "ラット大腸癌吻合部治癒における術後栄養補給の効果"外科と代謝・栄養. 35・5. 309-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Witte MB, Kiyama T, Barbul A.: "Nitric oxide enhances experimental wound healing in diabetes."Br J Surg. 89(12). 1594-1601 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyama T, Tajiri T, Tokunaga A, Yoshiyuki T, Barbul A.: "Tacrolimus enhances colon anastomotic healing in rats."Wound Repair Regen. 10(5). 308-313 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyama T, Onda M, Tokunaga A, Efron DT, Barbul A.: "Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats."J Gastrointest Surg. 5(3). 303-311 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyama T, Onda M, Tokunaga A, et al.: "The effect of postoperative nutritional support on colon anastomotic healing in rats."Japanese Journal of Surgery, Metabolism and Nutrition.. 36. 185-190 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyama T, Tajiri T, Tokunaga A, Yoshiyuki T et al.: "The post-operative metabolic influence of tacrolimus."Japanese Journal of Gastroenterological Surgery. 35. 1597 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyama T, Tajiri T, Tokunaga A, Yoshiyuki T et al.: "Role of the route of nutritional support on wound healing of rat trauma model."Japanese Journal of Surgery, Metabolism and Nutrition.. 35. 309-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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