Rader Erik P, Song Wook, Van Remmen Holly, Richardson Arlan, Faulkner John A
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2007, USA.
Exp Physiol. 2006 Jul;91(4):781-9. doi: 10.1113/expphysiol.2005.033043. Epub 2006 May 4.
A protocol of 75 lengthening contractions (LCP) administered to skeletal muscles of mice causes an initial force deficit owing to the mechanical disruption of sarcomeres and a reduction in calcium release from the sarcoplasmic reticulum. During the 3 days following the LCP, a 'sealing off process' and inflammatory response occurs. The reactive oxygen species (ROS) released by invading inflammatory cells produce a secondary force deficit that is more severe than the initial deficit. The timing of the infiltration of inflammatory cells and increase in force deficit relative to the sealing off process is not well documented. We tested the null hypothesis that following a lifetime of overexpression of the genes for the intracellular antioxidants manganese superoxide dismutase, copper zinc superoxide dismutase or catalase in transgenic mice, the force deficits 3 days following the administration of a 75 LCP to in situ extensor digitorum longus muscles are not different from those of wild-type mice. Following the LCP, the force deficits ranged from 39 to 59% for the muscles of transgenic mice that overexpressed the genes for intracellular antioxidants and were not different from the force deficit of 44% observed for muscles of wild-type mice. The results provide evidence that the ROS damage does not occur within the cytosol of the injured fibres. Apparently, the hypercontraction of sarcomeres and accumulation of vesicles seal off and protect the intact portions of damaged fibres, such that the ROS damage and repair occurs in the milieu of the necrotic segments that are continuous with the extracellular matrix.
对小鼠骨骼肌进行75次延长收缩（LCP）的方案会导致最初的力量不足，这是由于肌节的机械破坏以及肌浆网钙释放减少所致。在LCP后的3天内，会发生“封闭过程”和炎症反应。侵入性炎症细胞释放的活性氧（ROS）会产生比初始不足更严重的继发性力量不足。炎症细胞浸润的时间以及相对于封闭过程力量不足的增加情况，目前尚无充分记录。我们检验了一个零假设，即在转基因小鼠中，细胞内抗氧化剂锰超氧化物歧化酶、铜锌超氧化物歧化酶或过氧化氢酶的基因过表达一生后，对原位趾长伸肌进行75次LCP给药3天后的力量不足与野生型小鼠无异。LCP后，过表达细胞内抗氧化剂基因的转基因小鼠肌肉的力量不足在39%至59%之间，与野生型小鼠肌肉观察到的44%的力量不足没有差异。结果提供了证据，表明ROS损伤并非发生在受损纤维的胞质溶胶内。显然，肌节的过度收缩和囊泡的积累封闭并保护了受损纤维的完整部分，使得ROS损伤和修复发生在与细胞外基质连续的坏死节段环境中。
