Reed Patrick, Porter Neil C, Strong John, Pumplin David W, Corse Andrea M, Luther Paul W, Flanigan Kevin M, Bloch Robert J
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ann Neurol. 2006 Feb;59(2):289-97. doi: 10.1002/ana.20750.
We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered.
Unfixed biopsies of control and FSHD deltoid and biceps muscles, snap-frozen at resting length, were cryosectioned, indirectly immunolabeled with fluorescent antibodies to sarcolemmal and myofibrillar markers, and examined with confocal microscopy to localize the immunolabeled proteins. Glutaraldehyde-fixed samples were stained with heavy metals, embedded, thin-sectioned, and examined with electron microscopy to determine the relationship between the sarcolemma and the underlying myofibrils.
Confocal microscopy showed that some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underlying contractile apparatus. Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100 nm in controls to values as high as 550 nm in FSHD.
Our results show that the pathophysiology of FSHD includes novel changes in the organization of the sarcolemma and its association with nearby contractile structures and suggest that, as in other muscular dystrophies, the integrity of the sarcolemma may be compromised in FSHD.
我们检查了面肩肱型肌营养不良症（FSHD1A）患者骨骼肌的肌膜，以了解其组织结构以及与附近收缩结构的关系是否像其他小鼠和人类肌营养不良症那样发生改变。
对对照、FSHD三角肌和肱二头肌进行未固定活检，在静息长度下速冻，然后进行冷冻切片，用针对肌膜和肌原纤维标记物的荧光抗体进行间接免疫标记，并用共聚焦显微镜检查以定位免疫标记的蛋白质。用戊二醛固定的样本用重金属染色，包埋，制成超薄切片，并用电子显微镜检查以确定肌膜与下方肌原纤维之间的关系。
共聚焦显微镜显示，FSHD样本中肌膜处的一些结构与下方的收缩装置排列不齐。电子显微镜显示，肌膜与最近肌原纤维之间的距离显著增加，从对照组小于100纳米增加到FSHD组高达550纳米。
我们的结果表明，FSHD的病理生理学包括肌膜组织结构及其与附近收缩结构关联的新变化，并表明，与其他肌营养不良症一样，FSHD中肌膜的完整性可能受到损害。
