ELECTRIC FIELDS ON METABOLISM OF A CHRONIC WOUND MODEL

电场对慢性伤口模型代谢的影响

• 批准号: 2194628
• 负责人: ROBERT J GOLDMAN
• 金额: $ 8.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2194628
• 关键词: DNA; angiogenesis; blood lipoprotein biosynthesis; collagen; collagenase; electric field; extracellular matrix; fibroblasts; fibronectins; macrophage; protein biosynthesis; proteoglycan; skin; wound healing

Among the patients treated by Rehabilitation Medicine are those with decubitus and leg ulcers. These have significant morbidity, mortality and often are resistant to conventional treatment. The efficacy of electrotherapy is unsettled after decades of use and the possibility remains that a natural source of electricity within wounds(i.e., the "skin battery") may promote healing. We propose to elaborate the observation that fibroblasts decrease protein synthesis if exposed to electric fields comparable to endogenous fields. For this purpose, human dermal fibroblasts in type I collagen dermal "equivalent" matrices (DEM) are exposed to ionic currents. Initial results from our DEM model are promising. They suggests an increase in proliferation to electric fields of 20 mv/m, 10Hz.(p,01). (Most often synthesis and proliferation are reciprocal). Employing the same model, we propose a comprehensive study of the biochemical response of the DEM model to these electric fields. We plan radioisotope assays for DNA, proteoglycans, collagen, fibronectin and collagenase. Identifying the process most susceptible to electric effect, we will survey response to amplitudes and frequencies within the endogenous range. If the skin battery is important to wound healing, cells should be most sensitive at 1-10 Hz (i.e., down to 5-20 m/m). Early after wounding, fibroblasts undergo fibroplasia, and synthesis of proteoglycans and fibronectin. Later, collagen synthesis and neoangiogenisis peak. We will investigate the biochemical response of fibroblasts in DEM from 0 to 14 days after stimulation to see if these biosynthetic transformations occur in vitro. If they do, we will have compelling evidence that the skin battery help mediates the response in vivo. Lastly, we will investigate electric effects on early intracellular events that ultimately lead to proliferation and/or synthesis.

在接受康复医学治疗的患者中有 板球和腿部溃疡。 这些具有明显的发病率，死亡率 并且通常对常规治疗有抵抗力。 的功效 使用数十年后，电疗疗法不稳定和可能性 仍然是伤口内的自然电力（即 “皮肤电池”）可能会促进康复。 我们建议阐述成纤维细胞降低蛋白质的观察 合成如果暴露于与内源性场相当的电场。 为此，人类皮肤成纤维细胞在I型胶原皮肤上 “等效”矩阵（DEM）暴露于离子电流。 最初的 我们的DEM模型的结果是有希望的。 他们建议增加 到20 mV/m，10Hz。的电场增殖（P，01）。 （大多数 合成和增殖是相互的）。 我们采用相同的模型，提出了一项关于 DEM模型对这些电场的生化响应。 我们计划 针对DNA，蛋白聚糖，胶原蛋白，纤连蛋白和 胶原酶。 确定最容易受到电动的过程 效果，我们将调查对幅度和频率的响应 内源性范围。 如果皮肤电池对伤口愈合很重要， 细胞应在1-10 Hz时最敏感（即低至5-20 m/m）。 受伤后的早期，成纤维细胞经历纤维浮肿，并合成 蛋白聚糖和纤连蛋白。 后来，胶原蛋白合成和 新血管生成峰。 我们将研究 刺激后0至14天的DEM成纤维细胞查看是否存在 生物合成转化发生在体外。 如果他们这样做，我们将有 令人信服的证据表明，皮肤电池有助于介导 体内。 最后，我们将调查对早期的电作用 最终导致扩散和/或的细胞内事件 合成。