CHARACTERIZATION OF MECHANICAL BASED INJURY IN MUSCLE

肌肉机械损伤的特征

• 批准号: 6375286
• 负责人: GORDON J LUTZ
• 金额: $ 21.06万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-07 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375286
• 关键词: Anura; biomechanics; injury; mechanical stress; muscle cells; muscle contraction; muscle disorders; myofibrils; sarcolemma; sarcomeres

DESCRIPTION: (adapted from Investigator's abstract) When skeletal muscle is forcibly lengthened while activated (eccentric contraction), injury occurs to the muscle that is characterized by a rapid and prolonged loss in force-generating ability followed by delayed onset muscular soreness. Injury to skeletal muscle from eccentric contractions is an extremely common clinical condition that occurs as a result of vigorous exercise or other forms of normal and accidental muscle overuse. Although recent studies have provided some important insights into the cellular and biochemical adaptations that follow eccentric contraction-induced injury, the precise mechanical conditions, at the level of the sarcomere, that result in mechanical injury remain poorly understood. For example, studies from various animal models have reported conflicting results as to whether mechanical stress or strain is the primary determinant of muscle injury. Also, the precise influence of initial sarcomenre length and lengthening velocity on injury remains poorly characterized. Further, only indirect evidence exists as to whether fibers of a particular size and type are selectively predisposed to mechanical injury. Although it has been theorized that non-uniformity in sarcomere length during eccentric contractions leads to mechanical instability, sarcomere popping and subsequent injury, direct tests of this theory have been difficult to achieve. Our understanding on the mechanical basis of muscle injury has been limited because most studies have been performed on whole muscles. The problem with whole muscle preparations is that sarcomeric strain and mechanical stress in individual fibers cannot be measured directly or predicted accurately. In contrast, single isolated fibers allow for accurate measurement of sarcomere strain along the entire length of the cell, and thus permit precise correlations to be made between mechanical events and contractile performance. However, because single intact fibers are extremely difficult to isolate from mammalian muscle, single fiber studies in mammals are restricted to skinned fiber preparations, where the cell membrane is disrupted, drastically altering the fiber's mechanical properties and cell signaling pathways. In contrast to mammalian muscle, single intact fibers can be readily isolated from frog muscle that retain complete mechanical stability, making it possible to study mechanical injury in an intact cellular environment at the single fiber level. Thus, the purpose of this proposal is to study mechanical-based muscle injury during eccentric contractions using intact frog single fibers. The mechanics experiments will be performed while monitoring segment length and sarcomere length transients along the full length of the fiber, providing a very precise and high resolution correlation between mechanical events (fiber stress and sarcomeric strain) and muscle injury. The extent of sarcomere popping will also be evaluated. The mechanical events that result in injury will be related to fiber size and fiber type at the single fiber and individual segment level. The aged population is particularly susceptible to the debilitation effects of eccentric contraction-induced injury because of general muscle weakness and poor regenerative properties. An understanding of the precise mechanical conditions that result in muscle injury could lead to improvements in the development of preventative therapies and rehabilitation.

描述：（改编自研究者摘要）当骨骼肌 在激活时强行延长（离心收缩）， 肌肉的特点是快速和长期的损失， 产生力量的能力，然后是延迟发作的肌肉酸痛。受伤 骨骼肌离心收缩是一种非常常见的临床 由于剧烈运动或其他形式的正常运动而出现的状况 和意外的肌肉过度使用尽管最近的研究提供了一些 对随后的细胞和生化适应的重要见解 偏心性收缩引起的损伤，精确的机械条件，在 导致机械损伤的肌节水平仍然很差 明白例如，来自各种动物模型的研究已经报道， 关于机械应力或应变是否是主要的， 肌肉损伤的决定因素。此外，初始肌节的精确影响 长度和延长速度对损伤的影响仍不清楚。 此外，只有间接的证据存在，以确定是否纤维的特定 大小和类型选择性地倾向于机械损伤。虽然 在离心过程中肌节长度的不均匀性 收缩导致机械不稳定，肌节爆裂， 伤害，这一理论的直接测试已经很难实现。我们 对肌肉损伤的机械基础的理解是有限的， 大多数研究是在整个肌肉上进行的。整体的问题 肌肉准备是肌节应变和机械应力， 单个纤维不能直接测量或精确预测。在 相比之下，单个分离的纤维可以精确测量肌节 沿着细胞的整个长度应变，从而允许精确的 在机械事件和收缩性能之间建立相关性。 然而，由于单个完整的纤维极难分离， 哺乳动物肌肉，哺乳动物中的单纤维研究仅限于皮肤 纤维制剂，其中细胞膜被破坏， 纤维的机械性能和细胞信号通路。相比 在哺乳动物肌肉中，可以容易地从青蛙肌肉中分离出单个完整的纤维 保持完整的机械稳定性，使研究成为可能 在单纤维水平的完整细胞环境中的机械损伤。 因此，本建议的目的是研究机械性肌肉损伤 使用完整的青蛙单纤维进行离心收缩。力学 实验将在监测节段长度和肌节的同时进行， 沿着光纤的全长沿着的长度瞬变，提供了非常精确的 以及机械事件（纤维应力和 肌节拉伤）和肌肉损伤。肌节爆裂的程度也会 被评价。导致损伤的机械事件将与 纤维尺寸和纤维类型在单个纤维和单个段水平。的 老年人特别容易受到 由于全身肌肉无力引起的离心收缩引起的损伤， 再生性能差。对精密机械的理解 导致肌肉损伤的条件可能会导致改善 发展预防性治疗和康复。