天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (2): 154-157.doi: 10.11958/j.issn.0253-9896.2015.02.011

• 实验研究 • 上一篇    下一篇

司来吉兰对帕金森病模型大鼠黑质纹状体TH 及 GDNF 表达的影响

吕超男， 毛文静， 马原源， 刘斌△， 张晋霞， 孙静， 成晓华， 李世英   

  1. 河北联合大学附属医院神经内一科 （邮编063000）
  • 收稿日期:2014-03-07 修回日期:2014-10-17 出版日期:2015-02-15 发布日期:2015-02-27
  • 通讯作者: 刘斌 E-mail:liubintsh@126.com
  • 基金资助:
    河北省医学科学研究重点课题 （20130064）

Effects of Eldepryl on TH and GDNF expressions in substantia nigra and striatum in Parkinson’ s disease model in rat

  • Received:2014-03-07 Revised:2014-10-17 Published:2015-02-15 Online:2015-02-27
  • Contact: LIU Bin E-mail:liubintsh@126.com

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摘要： 摘要： 目的 观察司来吉兰对帕金森病 （PD） 模型大鼠黑质纹状体内酪氨酸羟化酶 （TH） 及胶质细胞源性神经营养因子 （GDNF） 表达的影响， 探讨司来吉兰对多巴胺能神经元的保护作用及机制。方法 72 只健康雄性 SD 大鼠随机分为对照组、 模型组和司来吉兰组， 每组均设 4 d 和 8 d 2 个亚组， 各 12 只。模型组和司来吉兰组采用颈背部皮下注射鱼藤酮制备 PD 模型， 对照组皮下注射等体积葵花油。之后司来吉兰组每日灌胃咪多吡 0.5 mg/kg， 模型组和对照组每日灌胃等体积生理盐水， 4 d 和 8 d 组分别连续灌胃 4 d 和 8 d。采用免疫组化法和 Western blotting 法检测黑质纹状体 TH 和 GDNF 表达水平。结果 免疫组化法和 Western blotting 法检测结果均显示， 对照组大鼠黑质纹状体可见多量 TH 阳性细胞表达和少量 GDNF 阳性细胞表达， 8 d 和 4 d 组差异均无统计学意义。模型组 TH 和 GDNF 阳性细胞表达均明显低于对照组 （均 P< 0.05）， 8 d 和 4 d 组差异均无统计学意义。司来吉兰组 TH 阳性细胞表达低于对照组而高于模型组， GDNF 阳性细胞表达高于对照组和模型组 （均 P<0.05）， 且 8 d 组均高于 4 d 组 （均 P < 0.05）。结论 司来吉兰可减轻PD 模型大鼠黑质纹状体多巴胺能神经元的损伤， 其作用机制可能与增加 GDNF 表达有关。

关键词: 帕金森病, 酪氨酸单氧化酶, 胶质细胞源性神经营养因子, 多巴胺, 单胺氧化酶抑制剂, 酪氨酸羟化酶, 司来吉兰

Abstract: Abstract: Objective To observe the effects of Eldepryl on expressions of tyrosine hydroxylase (TH) and glial cell line-derived neurotrophic factor (GDNF) in substantia nigra and striatum in Parkinson’ s disease (PD) and to explore the protective mechanism of Eldepryl on dopaminergic neuron . Methods Healthy male Sprague-Dawley (SD) rats (n=72) were randomly divided into control group, model group and Eldepryl group (n=24 in each group). Each group was divided random⁃ ly into 2 subgroups as 4 day treatment group and 8 day treatment group (n=12 in each subgrop). Pakinson’ s disease model was established by injecting rotenone subcutaneously back the neck, rats in the control group were injected with an equal vol⁃ ume of sunflower oil subcutaneously at the same location. Rats in the Eldepryl group were then given Eldepryl 0.5 mg·kg-1 in⁃ tragastrically every day for 4 or 8 consecutive days and rats in model group and control group were given an equal volume of saline instead. The expression of TH and GDNF in substantia nigra and striatum were detected by immunohistochemistry and Western blotting. Results Immunohistochemistry and Western blotting showed that strong expression of TH positive cells with little expression of GDNF positive cells were seen in substantia nigra and striatum in rats of control group, and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within control group. The expression of TH cells and GDNF were both significantly reduced in model group compared with those in control group (both P < 0.05), and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within each group. The ex⁃ pression of TH positive cells were significantly reduced in Eldepryl group compared with those in control group, and were sig⁃ nificantly increased compared with those in model group. The expression of GDNF positive cells were significantly increased in Eldepryl group compared with those in control group and model group (all P<0.05). And there were significantly more ex⁃ pression of TH positive cells and GDNF positive cells at subgroup of 8 day treatment compared with those at subgroup of 4 day treatment within Eldepryl group with (all P < 0.05). Conclusion These data suggest that Eldepryl can protect the dam⁃ age of dopaminergic neurons in substantia nigra and striatum of PD rats. And its therapeutic mechanism may be associated with increased expression of GDNF.

Key words: Parkinson&rsquo, s disease, tyrosine 3-monooxygenase, glial cell line-derived neurotrophic factor, dopamine, monoamine oxidase inhibitors, tyrosine hydroxylase, Eldepryl