Gao Yuan, Wang Shasha, Yi Anji, Kou Ruirui, Xie Keqin, Song Fuyong
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China; Linyi Center for Disease Control and Prevention, Beijing Road, Linyi, Shandong 276001, PR China.
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
Chem Biol Interact. 2014 Aug 5;219:76-82. doi: 10.1016/j.cbi.2014.05.016. Epub 2014 Jun 2.
Chronic exposure to carbon disulfide (CS₂) can induce polyneuropathy in occupational worker and experimental animals, but underlying mechanism for CS₂ neuropathy is currently unknown. In the present study, male Wistar rats were randomly divided into three experimental groups and one control group. The rats in experimental groups were treated with CS₂ by gavage at dosages of 200, 400 and 600 mg/kg/day respectively, six times per week for 6 weeks. The formation of autophagosomes and lysosomes in motor neurons of rat spinal cord was observed by transmission electron microscopy, the level of autophagy-related proteins, lysosome-associated membrane protein 1 (LAMP-1), and cathepsin B in spinal cord tissues was determined by Western blot analysis, and the activity of cathepsin B was measured by fluorescence assay. The results demonstrated that the number of lysosomes in motor neurons was markedly increased in CS₂-treated rats. In the meantime, the administration of CS₂ significantly increased the level of microtubule-associated protein light chain 3-II (LC3-II), Atg1, UVRAG and LAMP-1 in rat spinal cord. Furthermore, the content and activity of cathepsin B in rat spinal cord also showed a significant elevation. Taken together, this study suggested that CS₂ intoxication was associated with the activation of lysosomal degradative machinery, which might play a protective role against CS₂-induced neuronal damage.
长期接触二硫化碳（CS₂）可导致职业工人和实验动物发生多发性神经病，但CS₂所致神经病的潜在机制目前尚不清楚。在本研究中，将雄性Wistar大鼠随机分为三个实验组和一个对照组。实验组大鼠分别以200、400和600 mg/kg/天的剂量经口灌胃给予CS₂，每周6次，共6周。通过透射电子显微镜观察大鼠脊髓运动神经元中自噬体和溶酶体的形成，采用蛋白质免疫印迹分析测定脊髓组织中自噬相关蛋白、溶酶体相关膜蛋白1（LAMP-1）和组织蛋白酶B的水平，并用荧光分析法测定组织蛋白酶B的活性。结果表明，CS₂处理的大鼠运动神经元中溶酶体数量明显增加。同时，给予CS₂显著提高了大鼠脊髓中微管相关蛋白轻链3-II（LC3-II）、自噬相关蛋白1（Atg1）、含紫外线辐射抗性相关基因蛋白（UVRAG）和LAMP-1的水平。此外，大鼠脊髓中组织蛋白酶B的含量和活性也显著升高。综上所述，本研究提示CS₂中毒与溶酶体降解机制的激活有关，这可能对CS₂诱导的神经元损伤起到保护作用。
