EFFICACY OF MEMBRANE SEALING THERAPY IN RADIATION INJURY

许多研究结果表明，细胞 细胞膜是电离辐射损伤细胞的重要部位。 细胞膜是辐射诱导的自由基释放的主要目标。 根的制定有效的治疗策略， 电离辐射损伤（“辐射灼伤”）仍然是一个 重要的医学研究目标。大多数辐射防护策略是 以自由基清除剂为基础， 在曝光之前。我们已经发现，泊洛沙姆188，一种生物相容性 非离子表面活性剂，在辐射暴露后10分钟施用 诱导通过强γ辐射渗透的膜的密封 （附录一）。此外，我们还证明了泊洛沙姆188和 类似的分子，能够密封电穿孔和热 透化细胞质膜，导致细胞恢复 可行性（附录II和III）。我们建议量化剂量反应 γ射线照射与等离子体变化的关系 膜传输特性;确定选定的 表面活性剂对膜和活力照射后的分离 成人骨骼肌纤维;研究分离的 辐射膜封闭对细胞凋亡和坏死动力学的影响 在增殖细胞中;并检查这些治疗效果 表面活性剂用于预防骨骼肌原位坏死。主要 该项目的目标是定量描述 辐照对质膜转运特性的影响，并确定辐照是否 基于表面活性剂的细胞膜修复策略可以有效地 防止在毒性水平暴露于电离辐射后的组织坏死 辐照

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.