PROMOTION OF SURGICAL WOUND HEALING BY GROWTH FACTORS

通过生长因子促进手术伤口愈合

• 批准号: 3467453
• 负责人: THOMAS Anthony MUSTOE
• 金额: $ 11.36万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3467453
• 关键词: bleomycin; disease /disorder model; elasticity; fibroblast growth factor; growth factor; immunocytochemistry; laboratory rabbit; laboratory rat; macrophage; northern blottings; organ culture; platelet derived growth factor; protein biosynthesis; radiobiology; topical drug application; transforming growth factors; wound healing

Wound healing both in surgical incisions in the compromised patient and in leg ulcers and pressure sores represents a major national health problem. The long term objective of this proposal is to develop quantifiable wound healing models with major similarities to clinical wound healing problems, to promote wound healing in these models by topically applied growth factors, and to elucidate their mechanism of action with the intent of providing a rationale and method to promote healing in clinical situations where it would be of benefit. A surgical linear incision model will be evaluated quantifiably by tensometry to measure wound healing strength, as well as histologically, immunohistochemically and by vascular perfusion studies. Our findings that growth factors PDGF and TGFB promote healing will be extended and the potential angiogenic and healing effects of FGF will be examined. Most models altered by systemic agents including steroids, irradiation, chemotherapeutic agents and macrophage toxins will be examined both for their clinical applicability and to elucidate the mechanism of action of the growth factors on healing. The interaction with systemic agents that promote healing will also be examined. A rabbit ear full thickness would model with similarities to clinical ulcer and pressure sores will be characterized and the epithelization and granulation tissue quantified on histological sections. The ability of growth factors PDGF, EGF, TGFB will be analyzed. Blood vessel formation will be analyzed by vascular perfusion studies. Further analysis of cell proliferation, collagen content and type, collagenase production and glycosaminoglycan production will be carried out in vitro. The altered healing states of ischemic, and irradiation will be analyzed in parallel fashion. An in vitro model of wound healing in the rat mesentery developed in my lab will be utilized to analyze the ability of respective growth factors to promote healing under controlled conditions and correlate to in vivo healing. Histological and immunohistochemical technique will be utilized as well as collagen analysis, and cell proliferation studies to elucidate the mechanism of action. Northern blot analysis of mRNA levels of growth factors and other protoncogenes will be carried out in collaboration.

手术切口的伤口愈合 病人和腿部溃疡和压疮代表了一个主要的 国家健康问题。 这一长期目标 建议是开发可量化的伤口愈合模型， 临床伤口愈合问题的主要相似之处，以促进 在这些模型中通过局部应用生长的伤口愈合 因素，并阐明其作用机制与 目的是提供一个基本原理和方法，以促进愈合， 在临床上会有帮助。 将对手术线性切口模型进行定量评价 通过张力测定法测量伤口愈合强度，以及 组织学、免疫化学和血管灌注 问题研究 我们的研究结果表明，生长因子PDGF和TGFB促进 愈合将延长，潜在的血管生成和愈合 将研究FGF的作用。 大多数模型被系统性改变 包括类固醇、放射、化疗剂的药物 和巨噬细胞毒素将接受临床检查 适用性，并阐明的作用机制， 生长因子对愈合的影响 与全身性药物的相互作用 促进愈合的药物也将被检查。 兔耳全厚模型与 临床溃疡和压疮将被表征， 组织学上定量的上皮形成和肉芽组织 路段 生长因子PDGF，EGF，TGFB的能力将是 分析了 血管形成将通过血管造影进行分析。 灌注研究。 进一步分析细胞增殖， 胶原蛋白含量和类型，胶原酶的产生， 糖胺聚糖的生产将在体外进行。 的 改变缺血的愈合状态，照射将是 以并行方式分析。 建立了大鼠肠系膜创伤愈合的体外模型 在我的实验室将被用来分析各自的能力， 在受控条件下促进愈合的生长因子， 与体内愈合相关。 组织学和 也将使用免疫组织化学技术 胶原蛋白分析和细胞增殖研究，以阐明 作用机制。 mRNA水平的北方印迹分析 生长因子和其他原基因的研究将在 协作