摘要
目的 初步探讨 2 ,5 己二酮的神经毒性是否与微管含量有关。方法 Wistar雄性大鼠 ,2 ,5 己二酮 2 0 0和 4 0 0mg·kg- 1,ip ,连续 8周 (每周 5d) ,取大脑、脊髓、坐骨神经组织匀浆 ,制备各组织上清和沉淀 ,采用SDS PAGE和Western印迹方法检测α 管蛋白、β 管蛋白的相对含量。 结果 2 ,5 己二酮 2 0 0和 4 0 0mg·kg- 1,ip ,后大脑沉淀和上清中的管蛋白含量相当于对照组的 87%～ 114 % ,没有显著性变化。脊髓沉淀中管蛋白的含量为对照组的 88%～10 5 % ,2 0 0mg·kg- 1组上清中α 管蛋白、β 管蛋白的含量相当于对照组的 5 9% (P <0 .0 5 )和 4 7%(P <0 .0 1) ,4 0 0mg·kg- 1组为 12 6 % (P <0 .0 5 )和15 6 % (P <0 .0 1) ;坐骨神经沉淀中的含量相当于对照组的 88%～ 10 9% ,上清中的含量均明显降低(P <0 .0 1) ,相当于对照组的 2 2 %～ 70 %。结论2 ,5 己二酮导致大鼠脊髓和坐骨神经中管蛋白含量的变化 ,其含量改变与 2 ,5 己二酮的外周神经毒性有关。
AIM To investigate whether the alterations o f microtubule content are responsible for the neurotoxicity of 2,5-hexanedione. METHODS 2,5-hexamedione was administered by intraperitoneal i njec tion to Wistar rats with daily dose of 200 and 400 mg·kg -1 for continuous 8 weeks(five times every week). Cerebrum, spinal cord and sciatic nerve were excised and homogenized, then centrifuged to prepare the supernatant and pellet sample. The relative levels of α-tubulin and β-tubulin were determined by s odium dodecyl sulfate polyacrylamide gel electrophoresis and Western-blot. RESULTS The contents of α-tubulin and β-tubulin in the cerebrum wer e not obviously affected with the relative contents from 87%-114% of the contro l. For the spinal cord, they kept unaffected in the pellet, but dropped to 59% and 47% on the supernatant of 200 mg·kg -1 group, while they increased to 126% and 156% of the control in 400 mg·kg -1 group. In addition, 2,5-hex anedione intoxication dose-dependently reduced the tubulin content to 22%-70 % of the control in the supernatant of the sciatic nerve, while they kept unaffe cted in the pellet. CONCLUSION 2,5-hexanedione intoxication re sults in alternations of microtubule content, and the alternations might be rela ted to its peripheral neurotoxicity.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2004年第5期385-389,共5页
Chinese Journal of Pharmacology and Toxicology
基金
国家 973计划资助项目 (2 0 0 2CB5 12 90 7)~~
关键词
2
5-己二酮
微管
大脑
脊髓
坐骨神经
hexanedione
microtubules
cerebrum
spinal cord
sc iatic nerve
