Song Fuyong, Zhang Cuili, Yu Sufang, Zhao Xiulan, Yu Lihua, Xie Keqin
Institute of Toxicology, Shandong University, 44 West Wenhua Road, Jinan, Shandong, People's Republic of China.
Neurochem Res. 2007 Aug;32(8):1407-14. doi: 10.1007/s11064-007-9325-x. Epub 2007 Apr 20.
To investigate the mechanisms of the axonopathy induced by 2,5-hexanedione (2,5-HD), male Wistar rats were administered at a dosage of 400 mg/kg/day 2,5-HD (five times per week). The rats produced a slightly, moderately, or severely abnormal neurological changes, respectively, after 2, 4, or 8 weeks of treatment. The cerebrums were Triton-extracted and ultracentrifuged to yield a pellet fraction and a corresponding supernatant fraction. The relative levels of six cytoskeletal proteins (NF-L, NF-M, NF-H, alpha-tubulin, beta-tubulin, and beta-actin) in both fractions were determined by immunoblotting. The results showed that NFs content in HD-treated rats demonstrated a progressive decline as the intoxication of HD continued. As for microtubule proteins, the levels of alpha-tubulin and beta-tubulin demonstrated some inconsistent changes. The content of alpha-tubulin kept unchangeable, while the content of beta-tubulin increased significantly at the late stage of HD exposure. Furthermore, the content of beta-actin in both fractions remained unaffected throughout the study. These findings suggest that HD intoxication resulted in a progressive decline of NFs, which was highly correlated with the development of HD-induced neuropathy.
为研究2,5 -己二酮（2,5 - HD）诱导轴突病的机制，对雄性Wistar大鼠按400 mg/kg/天的剂量给予2,5 - HD（每周5次）。治疗2、4或8周后，大鼠分别出现轻度、中度或重度异常神经变化。将大脑用Triton提取并超速离心，得到沉淀部分和相应的上清部分。通过免疫印迹法测定两部分中六种细胞骨架蛋白（NF - L、NF - M、NF - H、α -微管蛋白、β -微管蛋白和β -肌动蛋白）的相对水平。结果显示，随着HD中毒持续，HD处理大鼠的神经丝（NFs）含量呈逐渐下降趋势。至于微管蛋白，α -微管蛋白和β -微管蛋白的水平表现出一些不一致的变化。α -微管蛋白含量保持不变，而β -微管蛋白含量在HD暴露后期显著增加。此外，在整个研究过程中，两部分中β -肌动蛋白的含量均未受影响。这些发现表明，HD中毒导致NFs逐渐下降，这与HD诱导的神经病变的发展高度相关。
