EFFICACY OF MEMBRANE SEALING THERAPY IN RADIATION INJURY

大量的研究结果表明，细胞 膜是电离辐射损伤细胞的重要部位。 细胞膜是辐射诱导游离的主要靶点。 激进分子。开发有效的治疗策略来治疗 电离辐射损伤(“辐射烧伤”)仍然是一种 重要的医学研究目标。大多数辐射防护策略是 基于自由基清除剂，如果给药是有效的 在曝光之前。我们发现泊洛沙姆188，一种生物相容的 非离子表面活性剂，在辐射暴露10分钟后使用 强伽马射线对渗透膜的封闭作用 (附录I)。此外，我们已经证明了泊洛沙星188和 类似的分子，能够封闭电穿孔和热 使细胞质膜通透性，导致细胞修复 生存能力(附录II及III)。我们建议将剂量反应量化 伽玛射线照射与血浆改变的关系 膜传输性能.测定所选的药效 表面活性物质对体外培养细胞照射后细胞膜及活性的影响 成人骨骼肌纤维；研究分离的 放射封膜对细胞凋亡和坏死动力学的影响 在细胞增殖中的作用；并检测这些药物的治疗效果 预防骨骼肌原位坏死的表面活性物质。少校 该项目的目标是定量地描述 辐射对质膜运输特性的影响 基于表面活性物质的细胞膜修复策略可以有效地在 预防中毒水平电离暴露后的组织坏死 辐射。

Numerous studies have produced results which indicate that the cell membrane is an important site of cell damage from ionizing irradiation. The cell membranes are a major target for radiation induced free radicals. Development of effective therapeutic strategies to treat ionizing radiation injuries ("radiation burns") continues to be an important medical research objective. Most radioprotectant strategies are based on free radical scavengers which are effective if administered before the exposure. We have found that poloxamer 188, a biocompatible non-ionic surfactant, applied ten minutes after radiation exposure induces sealing of membranes permeabilized by intense gamma irradiation (appendix I). In addition, we have demonstrated that poloxaner 188 and similar molecules, are capable of sealing electroporated and thermally permeabilized cell plasma membranes, resulting in restoration of cell viability (appendices ll & III). We propose to quantify the dose response relationship between gamma irradiation exposure and altered plasma membrane transport properties; determine the efficacy of selected surfactant agents on membrane and viability after irradiation of isolated adult skeletal muscle fibers; investigate the effects of isolated irradiation membrane sealing on the kinetics of apoptosis and necrosis in proliferating cells; and examine the therapeutic efficacy of these surfactants for prevention of skeletal muscle necrosis in situ. The major goals of this project are to quantitatively describe the effect of irradiation on plasma membrane transport properties and determine if surfactant based cell membrane repair strategies can be effective in preventing tissue necrosis following toxic level exposure to ionizing irradiation.