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: 3467455
• 负责人: THOMAS Anthony MUSTOE
• 金额: $ 5.81万
• 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/3467455
• 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.

伤口愈合均在手术切口处进行折衷 病人和腿部溃疡和压疮是一个主要的 国家健康问题。这样做的长期目标是 建议开发可量化的伤口愈合模型 与临床伤口愈合问题的主要相似之处，以促进 局部应用生长在这些模型中的伤口愈合 因子，并阐明其作用机制。 意在提供一个促进愈合的理论基础和方法 临床情况下，它将是有益的。 外科直线切开模型将被定量评估。 通过张力计测量伤口愈合强度以及 组织学、免疫组织化学和血管灌注法 学习。我们的研究发现，生长因子PDGF和TGFb促进 愈合时间将延长，潜在的血管生成和愈合 将检测成纤维细胞生长因子的作用。大多数模型都被系统更改 药物包括类固醇、辐射、化疗药物 巨噬细胞毒素将进行临床检测 并阐明其作用机制。 生长因子对愈合的影响。与系统性因素的相互作用 促进治愈的东西也将被研究。 一只全厚的兔耳模型与 临床溃疡和压疮的特征将是 上皮化和肉芽组织的组织学定量 横断面。生长因子PDGF、EGF、TGFb的能力将 分析过了。血管形成将通过血管进行分析 血流灌注研究。对细胞增殖的进一步分析， 胶原蛋白的含量和类型、胶原酶的产生和 糖胺多糖的生产将在体外进行。这个 缺血的愈合状态改变，而放射治疗会 以并行方式进行分析。 大鼠肠系膜创伤愈合体外模型的建立 在我的实验室中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和 与体内愈合有关。组织学和 将利用免疫组织化学技术以及 胶原蛋白分析和细胞增殖研究以阐明 作用机制。RNA水平的Northern印迹分析 生长因子和其他原癌基因的研究将在 协作。