The Molecular Basis of Muscular Dystrophy THE HUMAN PERSPECTIVE The Molecular Basis of Muscular Dystrophy The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 1.The muscular dystrophies comprise collection of 肌肉萎缩症 inherited neuromuscular disease characterized by 遗传的 神经肌肉的 muscle-fiber degeneration and resulting muscle 变性，变质,退化 weakness. One of these diseases ,called Duchenne 杜兴肌肉萎缩症 muscular dystrophy after the person who described it in 1861, The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy is a common ,debilitating disorder that strikes 逐渐衰弱的 病症，不舒 about 1 in 3,300 males. This is the disease that is most often associated with the name “muscular 相关联的 dystrophy,” and it is the primary subject of this 受检者 section. But there are several other rare types of Muscular dystrophy that have revealed interesting insights into the relationship 自知力，顿悟 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy between the cytoskeleton ,plasma membrane, and the extracellular matrix. We will begin with 细胞外基质 Duchenne muscular dystrophy (DMD). 2.The gene responsible for DMD is named dystrophin , and it has the distinction of being the 抗肌肉萎缩蛋白 largest gene so far identified in the mammalian 　　　　　　　　已鉴定的 哺乳动物的 　genome . 基因组 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy The gene stretches for more than 2.3 million bases along the X chromosome , a length that requires 16 hours to be transcribed into a single 转录 mRNA! Only about 0.6 percent of the gene actually codes for amino acids; the remaining 99.4percent consist of noncoding introns (Section 11.3) 基因内区 3.The protein encoded by the dystrophin gene reside in the membrane skeleton of striated muscle cells. 横纹肌的 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Like the related spectrin 血影蛋白molecules of the erythrocyte 红血球cytoskeleton (page 149), dystrophin molecules are rod-shaped dimers 杆状 二聚物 that lie just beneath the plasma membrane (Figure 1). The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy On their cytoplasmic side ,dystrophin molecules are attached to actin filaments, and on their 肌动蛋白 纤丝 束 membrane side, they are attached to a cluster of dystophin-associated proteins (DAPs), in turn, are linked on their extracellular surface to components of the basement membrane that surround these contractile cells. Taken together, 会收缩的，有收缩性的 these various proteins form a functional pathway linking the extracellular matrix with the internal cytoskeleton. The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy In addition, dystrophin provides structural support for the plasma membrane as the muscle fiber repeatedly contracts and relaxes. 4.DMD is a severe form of muscular dystrophy, which is characterized at the cellular level by the virtual absence of dystrophin molecules from both skeletal and cardiac muscle cells. A less 骨骼的 心脏的 severe form, called Becher muscular dystrophy , The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy also occurs ,in which the protein is present but is abnormal and/or greatly reduced in amount .The symptoms of DMD usually appear in childhood 症状 when the patient has difficulty performing certain motor tasks , such as climbing stairs or rising from a 启动的 工作 prone position .The disease progresses with 伏卧的 衰弱 increasing muscular weakness and debilitation ,finally taking the patient’s life as the result of respiratory or cardiac failure . 呼吸 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 5.Patients with DMD show dramatic abnormalities in both cardiac and skeletal muscle 反常 tissue . At the light microscopic level, some of the muscle fibers are seen to be degenerating 逐渐变形，变质 (necrotic) and often infiltrated by macrophages 坏死的 浸润 巨噬细胞 of the immune system. The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy At the electron microscopic level, segments of the plasma membrane are seen to be missing from the cell surface so that the extracellular basement membrane remains the primary encasement of the muscle fiber. As expected, 装箱 、 套 destruction of the plasma membrane is accompanied by marked internal changes in the cell , including the dilation of the sarcoplasmic 膨胀，扩张 原生质的 reticulum, The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy swelling of mitochondria , increased proteolytic 膨胀 （分）解蛋白的 digestion of cell materials , and rupture of （突然地）裂开 myofibrils. Damage to the plasma membrane is 肌原蛋白 apparently caused by mechanical stress exerted on it as the muscle contracts. This view is supported by the fact that the greatest damage occurs to those muscles in the body that are subjected to the greatest mechanic stress. 随着 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 6.Dystrophin is not the only gene that , when mutated ,can causer muscular dystrophy . Congenital muscular dystrophy (CMD) is a rare form 先天的 of the disease that develops in early infancy and strikes 婴儿时期，幼年 boys and girls with equal frequency . The disease has been traced to a deficiency in one of the subunits of the laminin molecule that forms a key component of the muscle cell casement membrane (Figure 1). The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Another form of the disease ,called severe childhood autosomal recessive 常染色体的 隐性的 muscular dystrophy (SCARMD), results from the absence of one of the subunits of the DAP complex (Figure 1). It is noteworthy that patients 值得注目的 with DMD, CMD, and SCARMD all exhibit severe forms of the disease, The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy indicating that all three components of the molecular chain-dystrophin ,DAP, and laminin-are required for muscle function. 7.At the present time, there is no treatment to stem 阻止 the degenerative changes that occur with any of the muscular dystrophies, and the best hopes of patients lie in the development of gene therapy in 治疗 which the defective gene is replaced by a normal version. The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Fortunately, several animal models of muscular dystrophy have been developed , including the mdxmouse ,which lacks a functional dystrophin 米德塞斯大学小鼠 gene .Unlike its human counterparts , these 极相似的东西 dystrophin-deficient mice show only mild 轻微的 symptoms. 症状 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Regardless, they are still useful models for testing new molecular-based therapies and screening （尤指不使用药物或不用手术的）疗法 屏蔽；普查 drugs that might have therapeutic value .Studies 治疗学的 on mdxmice have turned up one drug-an 发现 antibiotic called gentamicin-that causes the 抗生素 庆大霉素，艮他霉素 animals to synthesize dystrophin and protects them from muscle damage. The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Mdx mice fail to produce dystrophin because their dystrophin genes contain a mutation that leads to premature termination during synthesis 未成熟的，太早的 of the protein. Gentamicin reverses the effects of this 倒转 mutation by allowing the ribosome to read 允许 through the defect on the mRNA and produce a full-size dystrophin molecule .It is estimated that The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy approximately 15 percent of DMD patients fail to synthesize dystrphin because of a similar type of genetic defect. Clinical trials of gentamicin on 临床的 试验 members of this population are planned. 8.Another approach that has been tried in clinical trials on human patients-without measurable success-is cell transplantation therapy . The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy In these trials, normal, undifferentiated muscle 未分化的 cells ( myoblasts ) were isolated from muscle 成肌细胞 分离 tissue of close relatives and injected into particular muscles of the patient. It was hoped that the donor myoblasts would fuse with the genetically deficient cells of the patient and 缺失的 provide genetic messages for the production of The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy normal dystrophin throughout the entire muscle fiber . The survival rate of the injected cells was very low , and little or no evidence of the production of dystrphin was observed. 9.In recent years, a new approach to cell transplantation therapy has begun using injected bone marrow cells, rather than 骨髓 myoblasts . The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Blood forming tissues, such as bone marrow, contain stem cells that are capable of differentiating into muscle tissue( discussed on page 17) .When bone marrow cells from a healthy donor mouse are injected intravenously 静脉注射的 into an mdx mouse, a small percentage of the introduced cells make their way 导入的 一路前进，向前 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy into muscles throughout the recipient’s body and differentiate into dystrophin-producing muscle cells. To date, the effect on the 到此为止 muscle tissues of these dystrophic animals is not dramatic enough to provide much encouragement to human DMD patients ,but it dose represent a start towards new type of therapy . The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy It is hoped , one day ,that bone marrow cells can be removed from a DMD patient, provided with a normal copy of the dystrophin gene in vitro ,and then reintroduced into the patient to 试管内的 give rise to normal muscle tissue .Alternatively, DMD patient might receive bone marrow cells from a healthy, compatible donor .such cells 协调的，一致的 would contain the normal dystrophin gene The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy without having to be genetically altered, but the use of bone marrow from another individual raises problems of immune rejection that have to be 免疫排斥 considered. The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 人 类 展 望 —— 肌肉萎缩的分子基础 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 1. 肌肉的萎缩症包含了许多遗传性的神经肌肉的疾病，其特点是：即肌肉纤维的退化，并最终导致肌无力。其中有一种叫做杜氏肌肉萎缩症，它是于1861年首次被发现的，并以其发现者命名的，.这是一种普通的，逐渐衰弱的病症，并且每3300个男人中就有一人患有此病症。大多数时候这种病常与肌肉萎缩症联系在一起，它也是这一领域最初的受检者。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 但是也有其它几种肌肉萎缩症的稀有类型，他们揭示了有关细胞骨架、质膜和细胞制基质三者关系的认识。我们将从杜兴肌肉萎缩症（DMD）入手进行学习。 2. 应答DMD的基因被叫做抗肌肉萎缩蛋白,它的特性是：它是至今为止在已鉴定过的哺乳动物基因组中最大的一个。这个基因沿X染色体有230万个碱基，要将其转录为一个单链DNA要花费16小时！但事实上，他们中只有0.6%编码氨基酸，剩下的99.4%由非编码区构成。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 3.由dystrophin基因编码的蛋白质存在于有条纹的肌肉细胞的骨架膜上。 就像红细胞骨架上的血影蛋白一样，dystrophin分子是一种紧贴质膜下的杆状二聚物（如图）。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 在细胞质一侧，dystrophin分子与肌动蛋白纤丝相连；在膜一侧，他们与成束的dytrophin结合蛋白（DAPs）相连，并依次的与位于细胞外表面相连成为基膜的组成成分，环绕在有收缩性细胞的周围。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 所有这些各种各样的蛋白构成了连接细胞外基质和细胞内结构间的功能通道。除此之外，dystrphin作为肌肉纤维重复的收缩与舒张为原生质膜提供了结构上的支持。 DMD是一种非常严重的肌肉萎缩类型，他的发生在细胞水平表现为dystrphin分子在骨骼肌和心肌细胞中的缺失。另一种相对轻微些的疾病就是Becher肌肉萎缩症，这种病的发生不是因为dystraphin的缺失，而是因为它的变态或/和其分子数的骤降。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy DMD的症状通常在孩童时期就会出现，表现为：病人在做某些启动性运动时感到困难，如：爬楼梯，仰卧起坐。这种病会随着及肌肉的无力和衰弱而变得更糟，最终病人会因为呼吸系统和心脏的衰竭而死亡。 5. 患DMD的病人在心肌和骨骼肌系统中表现得相当反常。在显微水平，我们看到一些肌纤维会逐渐坏死，并且被免疫系统的巨噬细胞所浸润。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 在光学显微镜水平下，一些肌肉纤维退化并且经常被免疫系统的巨噬细胞所吞噬。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 在电子显微水平，我们看到细胞质膜的片断正在从细胞表面流失， 以至使细胞外肌膜成了主要的肌纤维外膜。 正如我们所预料的那样，质膜的破坏导致了细胞内部结构的显著变化， 包括：原生质网状结构的扩张，线粒体的膨胀，分解蛋白对细胞物质的消化增加，和肌原蛋白的破裂。 质膜的破裂很显然是由肌肉收缩时所产生的机械压力造成的。 这一观点是有事实依据的，通过实验人们发现，人体肌肉所承受的机械压力越大，其破坏程度越大。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 病因与发病原理 本病病因是遗传异常，在不同的类型中可以不同的方式进行，但遗传因素通过何种机制最终造成肌肉变性，则始终未明。目前认为可能由于遗传缺陷引起肌细胞膜形态结构异常，肌膜通透性及转运功能改变，使肌酶从胞浆中大量经肌膜“漏出”并使血清中有关酶相应增加；肌酶的外溢导致核糖体代偿性合成更多的肌酶，由于这种代偿作用相当有限，一定时间后肌细胞即遭受破坏，为增生的结缔组织取代。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 除肯定其为X-连锁隐性遗传病外，尚发现DMD基因座是在XP21（即X染色体短臂2区1带）上，另一个亚型BMD也是等位基因XP21基因缺陷导致骨骼肌中缺乏一种特异的抗肌萎缩蛋白（Dystrophin），导致肌管发育受阻、肌细胞再生能力差，造成肌管形态和功能上明显异常。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 病理 病变肌纤维肿胀，粗细不等，散布于正常纤维之间，肌横纹消失，有空泡形成、玻璃样变和颗粒变性，肌核增大增多且排列成链，肌纤维分裂，残存的肌纤维间有结缔组织增生及脂肪沉淀。疾病早期的肌纤维有再生现象，表现为肌浆的嗜碱染和肌核与核仁的增大、晚期病者，肌纤维极不规则，甚至消失，完全脂肪和结缔组织替代 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 电镜观察：最早有肌节内明支Z线模糊，同一肌源纤维的相邻几个明带受侵，明带间的间带基本正常，继而一条肌源纤维受累，病变继续发展则为大片肌源纤维溶解，继发神经纤维脱髓的改变。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Duchenne型营养不良症（DMD ） 也称严重性假肥大型营养不良症，几乎仅见于男孩，母亲若为基因携带者，50%男性子代发病，常起病于2-8岁，初期感走路苯拙，易于跌倒，不能奔跑及登楼，站立时脊髓前凸，腹部挺出，两足撇开，步行缓慢摇摆，呈特殊的“鸭步”步态，当由仰卧走立时非常困难，必先翻身俯卧，再双手攀缘两膝，逐渐向上支撑起立（Gower征），均由于骨盆带肌肉无力，萎缩，并波及髋、膝关节和足部的伸肌之故。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 随后病情发展累及肩胛带及上臂肌群则两臂不能上举，成翼状肩胛，最后肋间肌和面肌亦可无力，某些受累肌肉由于肌纤维被结缔组织和脂肪所替代而变得肥大坚实，此种“假性肥大”80%见于腓肠肌，亦可见于肢近端肌肉、股四头肌及臂肌。腱反射减低或消失，无感觉障碍。后期常由肌萎缩而致肌腱挛缩和关节强硬畸形，不少患儿尚伴有心肌病变，心电图可有P-R间期延长、Q波加深等异常。部分病儿智力低下。血清CPK明显增高，本病预后差，多数在20岁之前不能行走而卧床不起，常死于肺炎、心衰或慢性消耗。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy Becker型（BMD） 也称良性假肥大型肌营养不良症，常在10岁以后起病，首发症状为骨盆带及股部肌肉力弱，进展缓慢，病程长，出现症状后25年或25年以上才不能行走，多数在30-40岁时仍不发生瘫痪，预后较好，其血清CPK升高不如Duchenne型显著，肌肉组织化学染色可见ⅡB纤维，也与DMD不同。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 6. 当抗肌肉萎缩蛋白的基因发生突变时，人们发现它并不是引发肌肉萎缩症的唯一基因。先天肌肉萎缩症是一种罕见的疾病，它是在幼年时发生的，而且男女发病率相同。 这种病是由层粘连蛋白分子某亚基的缺失引起的，这个层粘连蛋白分子的亚基是肌细胞膜上的一个关键组分（如图）。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 这种病的另外一种形式叫做：儿童常染色体隐性肌肉萎缩症（SCARMD），是由DAP上的一个单位确实引起的。 值得注意的事，DMD, CMD,和SCARMD都表现出该病的严格症状，这表明分子链上的所有三种组分dystrophin，DAP和层粘连蛋白 都是肌肉功能所必需的。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 7. 现在还没有一种治疗方法，能阻止任何一种导致肌肉萎缩症的改变，患者最大的希望就落在了基因治疗方式的发展上了，通过这项技术，人们可以将缺陷基因取代而使分子恢复正常 。幸运的是，许多在患有肌肉萎缩症的动物模型身上所作的实验都有了很大突破。其中包括米德塞斯大学的一只缺少功能性dystrphin的小鼠。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 和人类不一样的是，这些小鼠抗肌肉萎缩蛋白的缺乏只导致轻微的症状。 不论如何，还是有一些有用的模型来应用于检测分子基础的治疗的新方法和进行药物的初筛。他们将是极具治疗学价值的。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 基因治疗 牛津大学分子医学研究所凯·戴维斯教授关于遗传性疾病进行性肌无力肌营养不良的研究工作发现，该病由基因缺陷所致，正常情况下，这种基因能够产生一种重要的蛋白质，被称为dystrophin蛋白。  戴威斯教授的研究表明，当dystrophin基因缺陷时，另外一种蛋白质utrophin能够替代它而在肌营养不良中发挥作用。她和其他人研究出一种新的基因治疗方法，即将utrophin产物转换进去从而取代丢失的或有缺陷的dystrophin蛋白。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 通过对米德塞斯大学小鼠的研究，人们发现了一种叫做庆大霉素的抗生素，它能使动物合成抗肌肉萎缩蛋白,并保护他们避免肌肉损伤。 米德塞斯大学小鼠不能产生抗肌肉萎缩蛋白是因为他们的抗肌肉萎缩蛋白的基因产生了突变，这种突变导致了蛋白质在成熟前就终止了合成。庆大霉素可以逆转这种突变带来的影响，因为它允许核糖体跨过缺陷来阅读mRNA，并产生抗肌肉萎缩蛋白分子。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 据估计，将近15%的DMD病人由于一种相似的遗传缺陷而不能合成抗肌肉萎缩蛋白。人们已经开始筹划对这类人群进行庆大霉素的临床试验。 8. 还有一种方法，已经在病人身上做过临床试验，但不是相当的成功，那就是细胞移植。在这种试验中，人们首先从病人近亲的肌肉组织中分离出正常的未分化的成肌细胞，然后将其注入病人的特殊细胞中。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 我们希望捐赠者的成肌细胞与病人的遗传缺失细胞相融，并为产生常态的抗肌肉萎缩蛋白提供遗传信息，这个抗肌肉萎缩蛋白将贯穿在完整的肌纤维中。然而注入细胞的成活率非常低，并且几乎观察不到有明显的抗肌肉萎缩蛋白产生。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 原因：假性肥大是肌肉细胞病变坏死以后，脂肪和结缔组织在病变的地方沉积导致的。这种情况各种进行性肌营养不良多少都有一点。培养的正常的肌肉细胞在脂肪和结缔组织里面无法生存。要么清除脂肪和结缔组织，要么寻找能穿凿破壁的肌肉细胞。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 9. 最近几年里，有一种用于细胞移植的新途径已经应用了，它植入的是骨髓细胞，而不是成肌细胞。像骨髓这种可以造血的组织都包含造血干细胞，具有分化形成肌肉组织的能力。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 当来自一只健康小鼠的干细胞被静脉注射到一只米德塞斯大学小鼠体内后，有一小部分的导入细胞一路前行，遍及受体（米德塞斯大学小鼠）的肌肉 ，并且分化出抗肌肉萎缩蛋白并产生肌细胞。至此，对这些患病动物肌肉组织的影响还不足以给DMD患者以鼓舞，但它使人们对产生另一种治疗新方法的希望 。人们期盼着终有一天，能从DMD患者升上提取干细胞，在试管内赋予它正常的dystrophin基因，然后将其重新植入患者体内，用来产生正常的肌肉组织。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy DMD患者已可以选择来自健康的、相匹配的捐赠人的干细胞。这些细胞含有正常的dustrophin基因，而不一定有遗传上的改变，但是对于其他个体的干细胞的应用，将会引起另一个问题——免疫排斥——这是我们必须要考虑的！ The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 最新进展 （2004年10月13日 09:44 来源: 信息时报） 中山大学附属第一医院利用脐血干细胞移植，进行基因治疗假肥大型肌营养不良症（DMD），首例名叫小虎的病孩已经初步获得临床成功，患者已经闯过了化疗预处理、脐血干细胞移植、粒细胞／血小板极度缺乏和急性排斥反应关。目前患病DMD基因已恢复正常！ The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 在异基因脐血干细胞移植等一系列手术完成后17天，干细胞植入检测证明小虎的供体细胞已经独立植入，到73天发现持续供体独立植入！ 小虎已经开始呈现良好的症状反应：术前要做摸鼻子动作时，他只能用头部挪动来迁就手指；但现在他已经可以用手去摸，腿部动作的幅度也比术前有所加大。医生表示，他的运动能力要经过一段较长时间后才能恢复。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy 肌营养不良症的预防： 肌营养不良症是一组原发于肌肉组织的遗传性变性疾病。因此:  ⑴遗传咨询，检测携带者，优生优育是预防本病发生的积极有效方法。患者的肌营养不良症的家族史应找医生（专科医生）作详细家谱分析。肌营养不良症四个型中假性肥大的杜氏型（DMD）对儿童健康危害最大。因此检测携带者对杜氏型（DMD）的预防和婚姻状况有很大指导意义。  The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy ⑵检测肌酸磷酸激酶（CPK）。肌营养不良假性肥大型患者血清中的肌酸磷酸激酶（CPK）增高，活性的测定可以查出部分病基因的可疑携带者。特别是杜氏患者大约有60-80%的肯定携带者和高度可疑携带者中肌酸磷酸激酶活性增高。 The Molecular Basis of Muscular Dystrophy

The Molecular Basis of Muscular Dystrophy ⑶产前明确定性别检测：产前确定性别对进行肌营养不良家属的高危胎儿有重要意义，女性携带者，男性患病者的肌营养不良症杜氏型（DMD）特点，因此可疑（DMD）携带者的产妇妊娠后期做羊水检查，以探测其基因位点有无突变；对杜氏欣（DMD）携带者孕妇确定为男孩，后应先用胎镜抽取胎儿血，检查肌酸磷酸激酶（CPK）或血清肌红蛋白（Mb）在决定是否终止妊娠。 The Molecular Basis of Muscular Dystrophy