CHARACTERIZATION OF MECHANICAL BASED INJURY IN MUSCLE

描述：(改编自调查人员摘要)当骨骼肌 在激活时被强制延长(偏心收缩)，发生损伤 一种肌肉，其特征是肌肉迅速而持久地丧失 力量生成能力随之而来的是延迟性肌肉酸痛。受伤至 骨骼肌的偏心性收缩是一种非常常见的临床现象。 由于剧烈运动或其他形式的正常运动而出现的状态 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低 明白了。例如，来自不同动物模型的研究报告 关于机械应力还是应变是主要原因的相互矛盾的结果 肌肉损伤的决定因素。此外，初始肌节的精确影响 损伤的长度和延长速度仍缺乏特征性。 此外，只有间接证据表明，特定的纤维是否 大小和类型选择性地易受机械性损伤。尽管它已经 理论上认为，在偏心运动中肌节长度不均匀 宫缩导致机械不稳定、肌节爆裂和随后 伤病，这一理论的直接检验已经很难实现。我们的 对肌肉损伤的力学基础的了解一直受到限制，因为 大多数研究都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 单独的纤维不能直接测量或准确预测。在……里面 相比之下，单个分离纤维可以准确测量肌节 沿细胞的整个长度进行应变，从而允许精确 机械事件和收缩性能之间的相关性。 然而，由于单一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 纤维准备，细胞膜被破坏，急剧改变 纤维的机械性能和细胞信号通路。与之形成鲜明对比的是 哺乳动物肌肉，单个完整的纤维可以很容易地从青蛙肌肉中分离出来 它们保持了完全的机械稳定性，使研究成为可能 在单一纤维水平的完整细胞环境中的机械损伤。 因此，本提案的目的是研究机械性肌肉损伤。 在使用完整的青蛙单一纤维进行偏心收缩时。机械学 实验将在监测节段长度和肌节的同时进行 沿光纤全长的长度瞬变，提供了非常精确的 和机械事件之间的高分辨率相关性(纤维应力和 肌节劳损)和肌肉损伤。肌节破裂的程度也会 被评估。导致受伤的机械事件将与 单纤维和单纤维段水平上的纤维尺寸和纤维类型。这个 老年人口特别容易受到 由于全身肌肉无力而导致的离心性收缩损伤 再生性能差。对精密机械的理解 导致肌肉损伤的情况可能会导致 发展预防性治疗和康复。

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.