Buchheim K, Stoltenburg-Didinger G, Lilienthal H, Winneke G
Neurologische Klinik und Poliklinik, Universitätsklinikum Charité, Humboldt-Universität Berlin, Germany.
Neurotoxicology. 1998 Aug-Oct;19(4-5):539-45.
Morphological changes in the central nervous system and other organs have been reported in numerous studies investigating low level lead exposure. To date, however, there are no investigations on the effect of low level lead exposure on striated muscles, although varying neuromuscular changes in different species have been known for years. Rhesus monkeys were exposed pre- and postnatally to lead acetate in the diet (350 ppm or 600 ppm) over 9 years, followed by a lead free period of 32 months, while a control-group received regular diet. No signs of muscular dysfunction were evident. To elucidate neuromuscular pathomorphology frozen sections of the vastus medialis muscle were processed for routine and enzymohistological staining (Hematoxilin and Eosin, Sudan Black, Gomori, NADH, ATPase). Resin histology was processed for electron microscopy. Morphometric analysis was made with commercial software. Light microscopy revealed dose-related signs of myopathy in the lead-exposed groups. The scatter of fibre diameters was increased, and split fibers and internal nuclei were more frequent. Fibres became separated from each other by copious endomysial connective tissue. Ultrastructural examination showed hydropic mitochondria and a massively dilated sarcotubular system in the 600 ppm group. Dose-related extracellular collagen deposition increased. A heavy fibrosis was seen in the 600 ppm group. These findings are interpreted as myopathical reaction due to chronic low level lead exposure, as there were no signs of neurogenical lesion. It remains unknown how the fibrosis developed. A primary fibrosis could be based upon a developmental delay of satellite cells (expressing metalloproteases for collagen-catabolism). Lead is known to inhibit regular development in many ways if exposure has started prenatally. As the skeletal muscle is a common target of toxicity, the myotoxic effects of chronic low level lead exposure comes into question.
在众多关于低水平铅暴露的研究中，均已报道了中枢神经系统和其他器官的形态学变化。然而，迄今为止，尽管不同物种多年来已知存在各种神经肌肉变化，但尚无关于低水平铅暴露对横纹肌影响的研究。恒河猴在出生前后9年通过饮食摄入醋酸铅（350 ppm或600 ppm），随后有32个月的无铅期，而对照组则接受常规饮食。未发现明显的肌肉功能障碍迹象。为阐明神经肌肉病理形态学，对股内侧肌的冰冻切片进行常规和酶组织化学染色（苏木精和伊红染色、苏丹黑染色、Gomori染色、NADH染色、ATP酶染色）。对树脂组织进行电子显微镜检查。使用商业软件进行形态计量分析。光学显微镜显示铅暴露组存在与剂量相关的肌病迹象。纤维直径的离散度增加，分裂纤维和内部细胞核更为常见。纤维因丰富的肌内膜结缔组织而彼此分离。超微结构检查显示，600 ppm组存在线粒体水肿和肌管系统大量扩张。与剂量相关的细胞外胶原沉积增加。在600 ppm组观察到严重纤维化。由于没有神经源性病变的迹象，这些发现被解释为慢性低水平铅暴露引起的肌病反应。纤维化如何发展尚不清楚。原发性纤维化可能基于卫星细胞（表达用于胶原蛋白分解代谢的金属蛋白酶）的发育延迟。如果在产前开始接触铅，已知铅会在许多方面抑制正常发育。由于骨骼肌是常见的毒性靶点，慢性低水平铅暴露的肌毒性作用值得关注。
