School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia.
Int J Biochem Cell Biol. 2011 Mar;43(3):290-4. doi: 10.1016/j.biocel.2010.11.005. Epub 2010 Nov 21.
Duchenne muscular dystrophy is a severe muscle wasting disease caused by a mutation in the gene for dystrophin--a cytoskeletal protein connecting the contractile machinery to a group of proteins in the cell membrane. At the end stage of the disease there is profound muscle weakness and atrophy. However, the early stage of the disease is characterised by increased membrane permeability which allows soluble enzymes such as creatine kinase to leak out of the cell and ions such as calcium to enter the cell. The most widely accepted theory to explain the increased membrane permeability is that the absence of dystrophin makes the membrane more fragile so that the stress of contraction causes membrane tears which provide the increase in membrane permeability. However other possibilities are that increases in intracellular calcium caused by altered regulation of channels activate enzymes, such as phospholipase A(2), which cause increased membrane permeability. Increases in reactive oxygen species (ROS) are also present in the early stages of the disease and may contribute both to membrane damage by peroxidation and to the channel opening. Understanding the earliest phases of the pathology are critical to therapies directed at minimizing the muscle damage.
杜氏肌营养不良症是一种严重的肌肉消耗疾病，由肌营养不良蛋白基因的突变引起——肌营养不良蛋白是一种细胞骨架蛋白，将收缩机制与细胞膜上的一组蛋白连接起来。在疾病的晚期，会出现严重的肌肉无力和萎缩。然而，疾病的早期阶段以细胞膜通透性增加为特征，这使得可溶性酶（如肌酸激酶）能够从细胞中漏出，离子（如钙）进入细胞。最广泛接受的解释增加细胞膜通透性的理论是，缺乏肌营养不良蛋白使细胞膜更加脆弱，以至于收缩产生的压力导致细胞膜撕裂，从而增加了细胞膜的通透性。然而，其他可能性是，通道调节改变导致细胞内钙离子增加，激活酶，如磷脂酶 A2，从而增加细胞膜通透性。在疾病的早期阶段也存在活性氧物质（ROS）的增加，这可能通过过氧化作用导致膜损伤，并导致通道开放。了解病理学的最早阶段对于针对最小化肌肉损伤的治疗至关重要。
