线粒体脑肌病患者的基因突变研究

目的 探讨线粒体脑肌病患者骨骼肌细胞线粒体DNA基因突变情况及发病机制。方法 观察总结5例线粒体脑肌病患者的临床表现,影像学变化特点,并应用PCR、限制性内切酶BglⅠ、ApaⅠ酶切,PAGE电泳鉴定DNA片段长度的方法,检测5例患者骨骼肌细胞中mtDNA是否发生nt3243和8344位点A→G突变。结果 5例患者（3例MELAS和2例MERRF）在临床表现和影像学改变等方面均与国外学者的研究结果相符。1例MELAS患者仅存在3243A→G点突变,1例MERRF患者存在8344A→G点突变,1例MERRF上述2个位点均存在突变。另2例呈家系起病的MELAS患者这2个位点都无突变。结论 3243及8344位点突变分别与MELAS和MERRF的发病有关,MERRF患者可以同时存在上述2个位点的突变。临床表现仍是确诊和分类的主要依据。Ⅰ     

线粒体肌病和脑肌病患者骨骼肌细胞线粒体DNA缺失分析

目的为了检测线粒体肌病和脑肌病患者的骨骼肌细胞的线粒体ＤＮＡ的缺失情况。方法从６例原发性线粒体肌病和１例脑肌病患者的骨骼肌活检标本中，提取总ＤＮＡ，以线粒体ＤＮＡ全长为探针进行分子杂交。结果发现１例ＭＥＲＲＦ患者有５ｋｂ的线粒体ＤＮＡ基因缺失，另１例线粒体肌病患者有１５ｋｂ的线粒体ＤＮＡ基因缺失，剂量分析表明缺失型线粒体ＤＮＡ分别占总线粒体ＤＮＡ的１９．３％和１０．７％。结论线粒体ＤＮＡ基因缺失是线粒体疾病的重要病因之一     

线粒体肌病和线粒体脑肌病组织化学及电镜的研究

本文报告了2例线粒体肌病、3例线粒体脑肌病(MALES1例、MER-RF2例)。所有病例的速冻连续切片的GT染色均见有RRF。在HE—NADH—TR、ATP酶、PAS、、磷酸化酶及SND染色中均见有RRF样增强纤维。细胞色素C氧化酶染色中有2例的切片出现阴性染色肌纤维、考虑为复合体Ⅳ活性低下,余3例染色正常。电镜下观察到除有大量形态异常的线粒体外,并在这些线粒体内见有结晶状、板层状及同心圆样的包涵体。     

线粒体肌病患者腓肠神经的形态计量学分析

对５例已经肌肉活检病理及生化检测证实的线粒体肌病患者的腓肠神经进行光镜及电镜观察，并用形态计量学方法对其进行分析，结果发现大口径的有髓纤维减少，有髓纤维面数密度减小，有髓纤维轴索直径与纤维外直径之比增大，轴索变性，并可见轴索和雪旺细胞浆中有增多的异常线粒体。     

线粒体肌病和脑肌病现状

线粒体肌病和脑肌病现状刘永刚（综述）熊先骥（校）线粒体是存在于每个细胞内的除了细胞核以外唯一含有独立的ＤＮＡ复制系统的细胞器，其主要功能是合成三磷酸腺苷，为细胞代谢提供充足的能量。线粒体肌病是一组由于线粒体结构和功能异常所致的疾病，病变以侵犯骨骼肌为...     

线粒体脑肌病研究新进展

线粒体疾病是指一组生化确认或怀疑线粒体功能缺陷的临床异源性多系统疾病。由于在所有组织中均有结构或功能异常线粒体DNA分布以及线粒体DNA异质性的特点，使线粒体疾病可累及肌肉、脑、心脏和其它器官。临床症状多种多样，以中枢神经系统受累为主者称线粒体脑肌病，以肌肉受累为主者称线粒体肌病。     

线粒体肌病与线粒体脑肌病的酶组织化学和超微结构改变

目的：探讨原发性线粒体肌病与脑肌病的病理特征及临床特点。方法：对11例原发性线粒体肌病与脑肌病患者的临床表现，酶组织化学及超微结构进行分析，结果：11例MGT染色均发现有不整红边纤维（RRF），其中单纯表现为肌无力的患者7例，合并中构神经系统受累者4例，RRF出现比例为6．4％－10．3％，电镜观察11例，9例表现为线粒体数目增多，形态异常，嵴排列紊乱等。均可见线粒体内类结晶状包涵体。2例线粒体改变只见数量增多，未见其他异常。结论：光镜下酶组化染色发现典型RRF，对线粒体肌病与脑肌病的初步论断有重要价值。电镜观察肌膜下线粒体异常增多且形态异常，特别是线粒体内类结晶状包涵体的出现，对本病的确诊有重要意义。     

线粒体肌病与线粒体脑肌病的临床分析

目的探讨神经肌肉系统线粒体病的发病机制、临床与病理特征及诊断。方法对7例确诊为线粒体病患者的临床表现、病理检查、实验室与影像学资料进行了回顾性分析。结果该组患者诊断为线粒体肌病3例,线粒体脑肌病4例;其中2例患者血乳酸水平升高;7例患者肌电图均有异常发现,肌肉活检均有特征性的改变;4例线粒体脑肌病患者头部影像学均有异常改变。结论线粒体病主要累及肌肉及中枢神经系统,诊断要求多种手段结合,以临床和病理表现为主,近年来基因方面的研究及影像学诊断发展迅速,目前对本病主要采取对症治疗。     

Lactate metabolism during exercise in patients with mitochondrial myopathy

Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10 matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial dysfunction, lactate was oxidized in muscle to the same extent as in healthy control subjects. This surprisingly high ability to burn lactate in working muscle with defective mitochondria, probably relates to the variability of oxidative capacity among muscle fibers. The data suggests that lactate is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function.     

A large-scale deletion of mitochondrial DNA in a case with pure mitochondrial myopathy and neuropathy

Here we report the findings from a male patient with myopathy and neuropathy, who has a large-scale deletion of the mitochondrial genome at nucleotides 6570–14150. In the patient’s history, muscle cramps with intermittent weakness and polyneuropathy with disturbed micturition were the predominant symptoms. Morphological examination of a muscle biopsy sample revealed numerous ragged red fibers and prominent paracrystalline intramitochondrial inclusions. The sural nerve biopsy sample disclosed a chronically progressive neuropathy, predominantly axonal in type with a minor demyelinating component. In previous studies the clinical symptoms mentioned above have been related to point mutations at various positions in the mitochondrial DNA (mtDNA). The present study is the first to describe a large (8 kb) deletion of the mtDNA which had apparently caused myopathy and polyneuropathy without encephalopathy. Received: 27 July 1995 / Revised, accepted: 4 December 1995     

线粒体肌病与其它神经肌病破碎红纤维的对比研究

为了探讨破碎红纤维（ＲＲＦｓ）对线粒体肌病的诊断价值，对线粒体肌病、多发性肌炎／皮肌炎（ＰＭ／ＤＭ）和脊髓性肌萎缩（ＳＭＡ）３组病人ＲＲＦｓ的形态特点和出现频率进行了对比研究，同时对３组病人线粒体的超微结构改变进行了对比观察。结果发现总ＲＲＦｓ出现频率线粒体肌病组３．０％～１５．２％，ＰＭ／ＤＭ组５．２％～１１．１％，ＳＭＡ组４．５％～４９％。线粒体肌病组以典型ＲＲＦｓ为主，ＰＭ／ＤＭ组以均匀红染纤维为主，ＳＭＡ组以红边纤维为主。线粒体的超微结构观察发现线粒体肌病组线粒体形态改变、嵴排列异常及嵴内包涵体多见，受累线粒体较多。ＰＭ／ＤＭ组和ＳＭＡ组线粒体主要改变是数量增多，形态变小，而外形改变和嵴排列异常少见。未见嵴内包涵体。本研究结果提示ＲＲＦｓ及出现频率不能作为诊断线粒体肌病的形态学标准，典型ＲＲＦｓ对线粒体肌病的诊断较有价值。电镜观察线粒体超微结构改变的不同特点有助于线粒体肌病的鉴别诊断     

Multiple sclerosis and mitochondrial myopathy: An unusual combination of diseases

A woman with definite multiple sclerosis (MS) and mitochondrial myopathy is described. There were widespread white matter lesions on magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) abnormalities and evoked response changes. Muscle biopsy showed ragged red fibres (RRFs) and cytochrome c oxidase (CoX) deficiency. Southern blot analysis revealed a large deletion of mitochondrial DNA (mtDNA). The patient may be affected by two unrelated diseases, MS and mitochondrial myopathy, but this combination has never previously been reported.     

二氧化锗诱导的线粒体肌病动物模型的发病机制的研究

目的建立线粒体肌病的动物模型，以探讨线粒体肌病的发病机制。方法利用二氧化锗喂养Ｗｉｓｔａｒ大鼠２４周，进行肌肉病理检查，测定生化功能及线粒体ＤＮＡ含量。结果线粒体肌病动物模型被建立，其细胞内自由基含量增多，线粒体ＤＮＡ拷贝数明显减少。结论可能有部分线粒体肌病由环境毒素引起，细胞内自由基含量增多是其重要的发病环节     

Cytochrome-C-oxidase deficiency in muscles of a floppy infant without mitochondrial myopathy

Summary A 4-month-old girl had hypotonia, muscle weakness and cardiomyopathy at birth and died at the age of 8 months from heart failure. Muscle biopsy showed normal muscle fibers, normal mitochondria and type II hypotrophy, in agreement with clinical and neurophysiological signs consistent with a suprasegmental lesion. Cytochrome-C-oxidase was the only respiratory chain enzyme that was profoundly decreased in the patient's muscle, but not in her brain, heart and cultured fibroblasts. We suggest that cytochrome-C-oxidase deficiency in skeletal muscle is not always associated with mitochondrial abnormalities and may not always indicate primary muscle pathology.This work was carried out under a grant of the Muscular Dystrophy Association, USA and research grant CT 81.00146.04 from the Consiglio Nazionale delle Ricerche, Italy