《中国康复理论与实践》 ›› 2013, Vol. 19 ›› Issue (11): 1001-1005.

• 论文 • 上一篇    下一篇

28 烷醇对6-羟基多巴胺致帕金森病大鼠的行为学作用及其机制研究

王涛1,乔洪文1,刘雁勇2,杨楠2,纪超2,陈彪1,左萍萍2   

  1. 1.首都医科大学宣武医院神经生物学研究室,北京市100053;2.中国医学科学院基础医学研究所药理室,北京市100730。
  • 收稿日期:2013-06-16 修回日期:2013-08-12 出版日期:2013-11-25 发布日期:2013-11-25

Effects of Octacosanol on Behavioral Impairments and Its Mechanism through Nerve Growth Factor Mediated Pathway in Parkinsonism Rats Induced with 6-hydroxydopamine

WANG Tao, QIAO Hong-wen, LIU Yan-yong, et al.   

  1. Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • Received:2013-06-16 Revised:2013-08-12 Published:2013-11-25 Online:2013-11-25

摘要: 目的观察28 烷醇对帕金森病模型大鼠的行为学改善作用与中脑水平神经生长因子(NGF)、神经生长因子前体(proNGF)及其各自受体表达的变化。方法将6-羟基多巴胺(6-OHDA)通过立体定位仪注入大鼠右侧纹状体,以28 烷醇17.5 mg/kg(低剂量组)、35 mg/kg (中剂量组)、70 mg/kg (高剂量组)进行干预。给药2 周后行阿朴吗啡诱导的旋转测试和平衡杆测试;TUNEL染色检测纹状体内的细胞凋亡情况;Western 印迹法检测caspase-3、NGF及其受体、proNGF 及其受体蛋白表达情况。结果与模型组相比,中剂量和高剂量组旋转试验和平衡杆实验成绩改善(P<0.05);高剂量组纹状体内凋亡小体减少(P<0.05),NGF及其受体TrkA 表达增高(P<0.05),proNGF及其受体sortilin 和p75NTR表达降低(P<0.05),caspase-3 表达减少(P<0.05)。结论28 烷醇可改善帕金森病大鼠病理行为。其神经保护机制可能是调节NGF介导的细胞存活通路和proNGF 介导的凋亡通路相关蛋白表达,进而减少神经细胞凋亡。

关键词: 帕金森病, 神经生长因子, 神经生长因子前体, 神经保护, 凋亡, 大鼠

Abstract: Objective To investigate the effects of octacosanol on the behavioral changes and its potential mechanism in 6-hydroxydopamineinduced Parkinsonism rats. Methods 6-hydroxydopamine-induced Parkinsonism rats accepted octacosanol orally in the dosage of 17.5mg/kg (low dose), 35 mg/kg (medium dose) and 70 mg/kg (high dose) for 2 weeks, and then assessed with rotating test and narrow beam test. The apoptosis cells were counted with TUNEL assay, and the expression of nerve growth factor (NGF), precursor of nerve growth factor (proNGF), as well as their receptors were detected with Western blotting. Results The achievement of behavioral tests significantly improved after administration of octacosanol (P<0.05), with the decrease of the apoptotic cells, more expression of NGF and its receptors TrkA, and less expression of caspase-3, proNGF and its receptors p75NTR and sortilin, especially at the dosage of 70 mg/kg (P<0.05). Conclusion Octacosanol may protect the neurol impairment from 6-hydroxydopamine through NGF mediated pathway to decrease the apoptosis.

Key words: Parkinson's disease, nerve growth factor, precursor of nerve growth factor, neuroprotection, apoptosis, rats