权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study for expression and function of matrix metalloproteinase on wound healing

基质金属蛋白酶在伤口愈合中的表达及功能研究

基本信息

批准号：
13671260
负责人：
KIYAMA Teruo
金额：
$ 0.83万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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.

由于缝合线通常从粘膜脱落，基质金属蛋白酶(MMPs)在胃肠道比皮肤更容易被诱导。应用基质金属蛋白酶抑制剂BE16627B和免疫抑制剂他克莫司(FK506)，研究基质金属蛋白酶在伤口愈合中的作用。对76只体重270-290g的SD大鼠，采用同样的手术方法，即结肠单层内翻吻合和左侧背部植入渗透泵(1003型，Alza，Palo Alto，CA)。动物被随机分配给BE16627B 10 mg，他克莫司，剂量为0.01，0.1或1.0 mg/kg/d，或仅在渗透泵内注射该溶液。BE16627B显著增加吻合口的结肠破裂压(16 0±12 vs 12 5±7，p&lt；0.0 5)和胶原的可溶性分数(0.2 7±0.0 1 vs 0.2 1±0.0 1，p&lt；0.0 1)。他克莫司显著增加结肠破裂压(分别为146±9,158±10,151±6；0.01，0.1和1.0 mg/kg/天)，高于对照组(119±7，p&lt；0.01)。对照组的胶原酶活性低于0.01 mg/kg/天(p&lt；0.05)，但他克莫司可剂量依赖性地降低胶原酶活性(p&lt；0.05)。这些结果表明，抑制基质金属蛋白酶活性增加了创面强度和胶原可溶部分的沉积。结果表明，在急性吻合口愈合过程中，他克莫司虽然降低了胶原浓度，但仍能增强伤口的强度。在胶原合成和胶原分解两个方面，伤口愈合机制还需要进一步的研究。