GDNF 对MPTP 诱导帕金森病小鼠黑质TH mRNA、 Ephrin B2、p-c-Jun 的影响

Effect of GDNF on TH mRNA, Ephrin B2 and p-c-Jun in substantia nigra of mice with MPTP-induced Parkinson disease

摘要:

目的 研究胶质细胞源性神经营养因子（GDNF）对1- 甲基-4- 苯基-1，2，3，6- 四氢吡 啶（MPTP）诱导帕金森模型小鼠黑质酪氨酸羟化酶（TH）、Ephrin B2、磷酸化c-Jun（p-c-Jun）表达的影 响，探索GDNF 治疗帕金森病的价值。方法 选取84 只小鼠并采用MPTP 复制帕金森病模型，选取72 只 模型复制成功的小鼠随机分为实验组和模型组，每组36 只；另随机选取36 只健康小鼠作为对照组。对实验 组小鼠右侧侧脑室注射GDNF，模型组和对照组小鼠注射等量生理盐水。10 d 后比较3 组小鼠TH 神经元变 化、检测TH mRNA、Ephrin B2 和p-c-Jun 蛋白的表达。结果 模型组和实验组毁损侧神经元数、神经纤 维密度少于对照组（P <0.05），实验组神经元数高于模型组（P <0.05）；模型组TH mRNA 表达水平低于对 照组和实验组（P <0.05）。模型组小鼠Ephrin B2、p-c-Jun 蛋白表达水平高于对照组和实验组（P <0.05）。 结论 GDNF 能够提高MPTP 诱导帕金森病模型小鼠黑质TH 表达，降低Ephrin B2 和p-c-Jun 蛋白表达， 进而对小鼠多巴胺能神经元产生保护作用，提示GNDF 可能在治疗人帕金森病上具有一定价值。

Abstract:

Objective To investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the expressions of tyrosine hydroxylase (TH) mRNA, Ephrin B2 and p-c-Jun in substantia nigra of mice with Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and to explore the value of GDNF in the treatment of Parkinson disease. Methods Parkinson 's rat model was established with MPTP. Then 72 model mice were randomly divided into an experimental group and a model group with 36 in each group. Additional 36 healthy mice were randomly selected as the control group. GDNF was injected into the right lateral ventricle in the experimental group, while normal saline was injected into the right lateral ventricle in the model group and the control group. The changes of TH mRNA, Ephrin B2 and p-c-Jun proteins were detected and the changes of TH neurons in three groups were compared after 10 d. Results The number of injured neurons was smaller and the nerve fiber density was lower in the model and experimental groups than in the control group (P < 0.05), and the number of neurons in the experimental group was larger than that in the model group (P < 0.05). The expression of TH mRNA in the model group was lower than that in the control group and the experimental group (P < 0.05). The expressions of Ephrin B2 and p-c-Jun in the model group were higher than those in the control group and the experimental group (P < 0.05). Conclusions Glial cell line-derived neurotrophic factor can protect mouse dopaminergic neurons, suggesting that it may have certain value in the treatment of human Parkinson disease.