二硫化碳对大鼠脊髓组织中微管和微丝表达的影响  

Alterations of microtubule and microfilament expression in spinal cord of carbon disulfide intoxicated rats

作　　者：潘光兵[1] 宋福永[1] 赵秀兰[1] 于丽华[1] 周贵珍[1] 谢克勤[1] 

机构地区：[1]山东大学公共卫生学院毒理学研究所,济南250012

出　　处：《中华劳动卫生职业病杂志》2007年第3期148-151,共4页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家“973”资助项目（2002CB512907）;国家自然科学基金资助项目（30271138）

摘　　要：目的初步探讨二硫化碳的神经毒性是否与微管、微丝含量变化有关及其机制。方法Wistar雄性大鼠随机分为2个二硫化碳染毒组和1个对照组，每组20只，染毒剂量分别300和500mg／kg，每周5次，连续12周，建立二硫化碳中毒性神经病模型。利用SDS-PAGE和Western Blotting方法检测大鼠脊髓组织中α-微管蛋白、β-微管蛋白和β-肌动蛋白的相对含量；并利用RT-PCR检测α-微管蛋白、β-微管蛋白和β-肌动蛋白的相应mRNA水平。结果二硫化碳染毒引起大鼠脊髓中β-微管蛋白和β-肌动蛋白含量明显改变。300和500mg／kg二硫化碳染毒动物的脊髓上清β-微管蛋白含量较对照分别升高了141％和158％差异有统计学意义（P〈0．01），β-肌动蛋白的含量分别升高了19％和32％差异有统计学意义（P〈0．01）。在脊髓沉淀中，β-微管蛋白含量较对照分别增加了107％和118％差异有统计学意义（P〈0．01），但β-肌动蛋白的含量无明显改变。与此同时，与对照组相比，300和500mg／kg二硫化碳染毒动物β-微管蛋白的mRNA水平分别升高了207％和212％差异有统计学意义（P〈0．01），β-肌动蛋白的mRNA水平升高了94％和91％差异有统计学意义（P〈0．01）。然而，α-微管蛋白在蛋白和mRNA水平均无显著性改变。结论二硫化碳染毒引起大鼠脊髓中微管和微丝蛋白表达发生了显著改变，这种改变可能与二硫化碳的外周神经毒性有关。Objective To investigate whether the alterations of microtubule and microfilament expression are responsible for the neurotoxicity of carbon disulfide. Methods Wistar rats were administered with carbon disulfide by gavage at a dosage of 300 or 500 mg/kg for continuous 12weeks （five times per week） Spinal cords of carbon disulfide-intoxicated rats and their age-matched controls were Triton-extracted and ultracentrifuged to yield a pellet and a corresponding supernatant fraction. Then, the contents of α-tubulin, β-tubulin, and β-actin in both fractions were determined by immunoblotting. In the meantime, their mRNA levels in spinal cords were quantified using reverse transcriptase-polymerase chain reaction （RT-PCR）. Results In the supematant fraction, the contents of β-tubulin and β-actin in both treated groups increased significantly （P〈0.01）： the content of β-tubuiin increased by 141% and 158% respectevely, and the content of β-actin increased by 19% and 32% respectively. In the pellet fraction, the content of β-tubulin in both groups increased by 107% （P〈0.01） and 118%（P〈0.01） respectively, and the others keep unaffected. In the meantime, the levels of of mR- NA expression of β-tubuiin and β-actin gene were elevated consistently in CS2-treated groups （P〈0.01）： the levels of mRNA expression of β-tubulin increased by 207% and 212% respectively, and the levels of mRNA expression of β-actin increased by 94% and 91% respectively. Conclusion Carbon disulfide intoxication resuits in alternations of microtubule and microfilament expression, and the alternations might be related to its neurotoxicity.

关 键 词：二硫化碳 微管 微丝 神经病学表现 

分 类 号：R686[医药卫生—骨科学]