McNeil P L, Khakee R
Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, Massachusetts 02115.
Am J Pathol. 1992 May;140(5):1097-109.
The authors have tested the hypothesis that plasma membrane disruptions are an early form of structural damage to the fibers of eccentrically exercised muscle. Rat serum albumin (RSA) was used as a marker for muscle-fiber wounding in the rat tricep (medial head) exercised eccentrically by downhill running. In all muscles examined, strong staining with a horseradish peroxidase (HRP)-conjugated anti-RSA antibody was observed between fibers (intercellular staining) and also within certain fibers (intracellular staining). This intracellular staining was interpreted as identifying muscle fibers wounded at their plasma membranes and hence rendered transiently or permanently permeable to extracellular RSA. The most striking finding of this study was a 6.9-fold increase relative to unexercised controls in the number of wounded cells in the medial head immediately after eccentric exercise. The authors also reproducibly observed, albeit less frequently, myocytes that stained with anti-RSA in the medial head and several other muscles of the "unexercised," caged laboratory rat. The extreme vulnerability of muscle plasma membranes to mechanically induced stress was revealed in this study by HRP injections into the triceps long head. A single injection of 200 microliters HRP through a 26-gauge needle resulted in extensive labeling of the muscle fibers present in the long head cross-sectioned at the injection site. The authors propose that initially resealable and/or highly localized, unsealable membrane wounds are an early form of exercise-induced damage that could progress along the length of the fiber until, 1 to 4 days after eccentric exercise, it becomes sufficiently severe that it can be readily recognized as the frank fiber necrosis and cellular infiltration described in numerous previous studies. In possessing cells wounded at their plasma membranes, normal, undisturbed rat muscle and eccentrically exercised muscle appears to resemble gut and skin, two additional tissues routinely exposed to mechanical forces in vivo. The authors propose that membrane disruptions provide a route into and out of myofiber cytoplasm distinct from the conventional, membrane-bounded routes of endo- and exocytosis, and therefore may be of importance both technically, as a route for introducing foreign genes into muscle cells, and biologically, as a route for release of the growth factor, basic fibroblast growth factor.
质膜破裂是离心运动肌肉纤维结构损伤的早期形式。将大鼠血清白蛋白（RSA）用作大鼠三头肌（内侧头）通过下坡跑进行离心运动时肌肉纤维损伤的标志物。在所有检查的肌肉中，用辣根过氧化物酶（HRP）偶联的抗RSA抗体进行染色时，在纤维之间（细胞间染色）以及某些纤维内部（细胞内染色）均观察到强染色。这种细胞内染色被解释为识别在其质膜处受伤的肌肉纤维，因此使其对细胞外RSA具有瞬时或永久通透性。这项研究最引人注目的发现是，离心运动后立即在内侧头受伤细胞数量相对于未运动对照增加了6.9倍。作者们还反复观察到，尽管频率较低，但在“未运动”的笼养实验大鼠的内侧头和其他几块肌肉中，有肌细胞被抗RSA染色。通过将HRP注射到三头肌长头中，本研究揭示了肌肉质膜对机械诱导应激的极端脆弱性。通过26号针头单次注射200微升HRP，导致在注射部位横切的长头肌纤维出现广泛标记。作者们提出，最初可重新封闭和/或高度局部化、不可封闭的膜损伤是运动诱导损伤的早期形式，这种损伤可能会沿着纤维长度发展，直到离心运动后1至4天，损伤变得足够严重，以至于能够很容易地被识别为众多先前研究中所描述的明显的纤维坏死和细胞浸润。正常、未受干扰的大鼠肌肉和离心运动后的肌肉在质膜处有受伤的细胞，这似乎类似于肠道和皮肤，这是另外两种在体内经常受到机械力作用 的组织。作者们提出，膜破裂提供了一条进出肌纤维细胞质的途径，这与传统的、有膜包被的胞吞和胞吐途径不同，因此在技术上，作为将外源基因引入肌肉细胞的途径，以及在生物学上，作为生长因子碱性成纤维细胞生长因子的释放途径，可能都具有重要意义。
