Pezeshkpour G, Illa I, Dalakas M C
Neuromuscular Pathology Division, Armed Forces Institute of Pathology, Washington, DC.
Hum Pathol. 1991 Dec;22(12):1281-8. doi: 10.1016/0046-8177(91)90112-3.
Electron microscopic features of muscle biopsies from 13 human immunodeficiency (HIV)-positive patients who had myopathy while receiving zidovudine (AZT) were compared with biopsies from five patients with HIV-induced myopathy who were not treated with AZT. All specimens showed disorganization of the myofibrillar structures, along with a varying degree of nemaline (rod) bodies, vacuolization, inflammation, and endothelial tubuloreticular profiles. One untreated and all AZT-treated patients had cytoplasmic bodies, which in the latter were abundant, large, and irregular. Two untreated patients had a peculiar osmiophilic destruction of the muscle fibers, with numerous tubuloreticular profiles in the endothelial cells and brisk inflammation that included lymphoplasmatoid cells. The AZT-treated group had ubiquitous abnormal mitochondria that complemented the presence of ragged red fibers seen by light microscopy. There was subsarcolemmal proliferation of mitochondria, with marked variation in size and shape and proliferation or disorganization of their cristae. Paracrystalline inclusions were seen in one patient. Blind re-examination of the electron micrographs showed abnormal mitochondria that readily distinguished patients with AZT-associated myopathy from those with untreated HIV-induced myopathy. Immunocytochemistry using antibodies to single- and double-stranded DNA revealed severe reduction of mitochondrial DNA compared with the normal nuclear DNA. Although the myopathies associated with HIV and AZT share common myopathologic features, the mitochondrial abnormalities are unique to the AZT-treated patients. Since mitochondrial DNA is specifically reduced, the structural changes noted on electron microscopy are probably associated with mitochondrial dysfunction. Zidovudine, a DNA chain terminator that inhibits the mitochondrial gamma-DNA polymerase, is toxic to muscle mitochondria.
将13例接受齐多夫定（AZT）治疗期间出现肌病的人类免疫缺陷病毒（HIV）阳性患者的肌肉活检组织的电子显微镜特征，与5例未接受AZT治疗的HIV诱导性肌病患者的活检组织进行了比较。所有标本均显示肌原纤维结构紊乱，伴有不同程度的线状体（杆状体）、空泡化、炎症和内皮细胞管网状结构。1例未治疗患者和所有接受AZT治疗的患者均有胞质体，在接受AZT治疗的患者中胞质体丰富、体积大且形态不规则。2例未治疗患者出现肌纤维特有的嗜锇性破坏，内皮细胞中有大量管网状结构，炎症活跃，包括淋巴浆细胞。接受AZT治疗的组中普遍存在异常线粒体，这与光学显微镜下所见的破碎红纤维相符。线粒体在肌膜下增殖，大小和形状有明显差异，嵴有增殖或紊乱。1例患者可见副晶体包涵体。对电子显微镜照片进行盲法重新检查发现，异常线粒体可轻易将AZT相关肌病患者与未治疗的HIV诱导性肌病患者区分开来。使用单链和双链DNA抗体进行免疫细胞化学分析显示，与正常核DNA相比，线粒体DNA严重减少。尽管与HIV和AZT相关的肌病有共同的肌病理特征，但线粒体异常是接受AZT治疗患者所特有的。由于线粒体DNA特异性减少，电子显微镜下观察到的结构变化可能与线粒体功能障碍有关。齐多夫定是一种DNA链终止剂，可抑制线粒体γ-DNA聚合酶，对肌肉线粒体有毒性。
