CHARACTERIZATION OF MECHANICAL BASED INJURY IN MUSCLE

肌肉机械损伤的特征

• 批准号: 6030054
• 负责人: GORDON J LUTZ
• 金额: $ 26.18万
• 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/6030054
• 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：（改编自研究者的摘要）当骨骼肌 激活时强行拉长（偏心收缩），会造成伤害 肌肉的特点是快速而长期的损失 产生力量的能力，随后出现延迟性肌肉酸痛。受伤 偏心收缩引起的骨骼肌损伤是一种极其常见的临床症状 由于剧烈运动或其他形式的正常现象而发生的情况 以及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 明白了。例如，来自各种动物模型的研究报告 关于机械应力还是应变是主要因素的结果相互矛盾 肌肉损伤的决定因素。此外，初始肌门的精确影响 损伤时的长度和延长速度仍不清楚。 此外，仅存在间接证据来证明特定纤维是否 尺寸和类型选择性地容易受到机械损伤。虽然它有 理论上认为，偏心期间肌节长度不均匀 收缩导致机械不稳定、肌节爆裂等 伤害，这一理论的直接检验一直难以实现。我们的 对肌肉损伤机械基础的了解一直有限，因为 大多数研究都是针对整个肌肉进行的。整体的问题 肌肉准备是肌节应变和机械应力 单个纤维无法直接测量或准确预测。在 相比之下，单个孤立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 机械事件和收缩性能之间的相关性。 然而，由于单个完整纤维极难分离 哺乳动物肌肉，哺乳动物单纤维研究仅限于带皮 纤维制剂，其中细胞膜被破坏，极大地改变 纤维的机械性能和细胞信号传导途径。相比之下 哺乳动物的肌肉，可以很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，使得研究成为可能 在单纤维水平上的完整细胞环境中的机械损伤。 因此，该提案的目的是研究基于机械的肌肉损伤 在偏心收缩期间使用完整的青蛙单纤维。力学 将在监测节段长度和肌节的同时进行实验 沿光纤整个长度的长度瞬变，提供非常精确的 以及机械事件（纤维应力和 肌节拉伤）和肌肉损伤。肌节弹出的程度也会 进行评估。导致伤害的机械事件与 单根纤维和单个段级别的纤维尺寸和纤维类型。这 老年人口特别容易受到以下因素的影响： 由于全身肌肉无力和偏心收缩引起的损伤 再生特性差。对精密机械的理解 导致肌肉损伤的情况可能会导致改善 预防性治疗和康复的发展。