《中国康复理论与实践》

《中国康复理论与实践》 ›› 2012, Vol. 18 ›› Issue (9): 820-823.

• 论文 • 上一篇    下一篇

28 醇对MPTP 致帕金森病模型小鼠行为学的作用及其机制

王涛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100005。
  • 收稿日期:2012-05-28 修回日期:1900-01-01 出版日期:2012-09-25 发布日期:2012-09-25
  • 通讯作者: 左萍萍

Effects of Octacosanol on Behavioral Impairments and Its Mechanism through MAPKs Pathway in MPTP-treated Mice

WANG Tao, LIU Yan-yong, YANG Nan, et al   

  1. Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • Received:2012-05-28 Revised:1900-01-01 Published:2012-09-25 Online:2012-09-25

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摘要： 目的观察28 醇对帕金森病模型小鼠行为学改善作用，并探讨其可能的机制。方法75 只成年雄性C57 小鼠随机分为5 组：对照组，模型组，28 醇低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高剂量组(100 mg/kg)，每组15 只。除对照组外，其他各组间隔2 h 腹腔注射MPTP 16 mg/kg 共4 次造模。28 醇各剂量组按剂量连续灌胃给药2 周，其他组给予等量0.5%缩甲基纤维素钠(CMC)无菌水。行为学检测采用转杆试验和自发运动试验，Nissl 染色组化实验检测纹状体神经元数量及状态，Western blot 实验检测黑质区p-Erk1/2、p-p38 MAPK、p-JNK表达。结果与对照组相比，28 醇高剂量组转杆试验和自发运动试验成绩改善(P<0.05)。28 醇中剂量和高剂量组含有Nissl 小体的神经元显著增多并染色加深(P<0.05)，黑质区p-p38 MAPK、p-JNK蛋白表达与模型组相比下降(P<0.05)，p-Erk1/2 表达与模型组无显著性差异。结论28 醇可改善帕金森病小鼠行为学指标。可能通过调节MAPKs 家族信号转导因子p-p38 MAPK、p-JNK蛋白表达，减少黑质纹状体通路的损伤发挥其作用。

关键词: 帕金森病, 神经保护, 行为学, 丝裂原活化蛋白激酶, 28 醇

Abstract: Objective To investigate whether octacosanol would attenuate neurotoxicity in 1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Methods Behavioral tests, Nissl histochemistry and Western blot were used to investigate the effects of octacosanol in this mouse model of PD. Results Oral administration of octacosanol (100 mg/kg) significantly improved behavioral outcome in mice induced by MPTP and markedly ameliorated morphological appearances of neuronal cells in striatum. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. Conclusion The protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38 MAPK and JNK on the signal transduction in vivo.

Key words: Parkinson's disease, neuroprotecion, behavior, mitogen-activated protein kinases, octacosanol