MUSCLE RESPONSE TO STRESS IN CANINE MUSCULAR DYSTROPHY

该项目将为申请人提供研究技能 需要开发和评估康复治疗， 肌肉萎缩症患者的功能。在整个博士 在生理学计划，一个主要部分的努力将致力于一个 指导研究项目，将审查之间的关系， 机械应力和肌肉纤维损伤的犬同源物 杜氏肌营养不良症。这项研究的核心假设是 肌营养不良蛋白缺乏肌肉中的纤维损伤部分是由于 对机械应力的过度反应， 收缩。此外，参与延长收缩的肌肉 比其他肌肉承受更大的压力， 受伤了 将在选定的后肢中检验中心假设 通过评估细胞和生理指标， 肌纤维对不同水平的施加应力的反应特征。 虽然mdx鼠标更容易获得， 使用实验模型，营养不良的狗表现出临床特征 类似于患有杜氏肌营养不良症的人类。 目标1将 将肌膜损伤与肌纤维坏死联系起来：Aim 2将 比较参与延长的肌肉的再生特征 收缩与肌肉参与缩短收缩：目的3 将确定是否存在压力引起的损伤的较低阈值， 与对照组相比，营养不良纤维：Aim 4将确定 在生长过程中减小机械应力将消除或减小 在成人中观察到过度的纤维坏死和重塑 腓肠肌 预计调查结果将改善 了解营养不良的肌肉如何应对身体压力 从而改善了杜氏肌营养不良患者的治疗， 营养不良

This project will provide the applicant with the research skills required to develop and assess rehabilitation treatments that enhance function for patients with muscular dystrophy. Throughout a doctoral program in physiology, a major portion of effort will be devoted to a mentored research project which will examine the relationship between mechanical stress and muscle fiber injury in a canine homolog of Duchenne muscular dystrophy. The central hypothesis of this research is that fiber damage in dystrophin-deficient muscle results, in part, from an exaggerated response to mechanical stress incurred during contraction. Furthermore, muscles involved in lengthening contractions are subject to greater stress than other muscles, and are preferentially injured. The central hypothesis will be tested in selected hindlimb muscles of dystrophic dogs by evaluating cellular and physiological features of muscle fiber response to varying levels of imposed stress. Although the mdx mouse is more readily available and a more commonly used experimental model, the dystrophic dog expresses clinical features analogous to humans with Duchenne muscular dystrophy. Aim 1 will correlate muscle membrane damage with myofiber necrosis: Aim 2 will compare regenerative features in muscles involved in lengthening contractions with muscles involved in shortening contractions: Aim 3 will determine if a lower threshold to stress-induced injury exists in dystrophic fibers compared to controls: and Aim 4 will determine if reducing mechanical stress during growth will eliminate or decrease the exaggerated fiber necrosis and remodeling seen in the adult gastrocnemius muscle. It is anticipated that findings will improve the understanding of how dystrophic muscle responds to physical stress resulting in improved treatment for patients with Duchenne muscular dystrophy.