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山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (4): 32-36.doi: 10.6040/j.issn.1671-7554.0.2015.1321

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侧脑室注射腺病毒介导的GDNF基因对帕金森病的保护作用

王思1,2,李秀华2,杜鹃3,岳龙涛3,王瑶3,刘菲2,郭配1,2   

  1. 1.潍坊医学院, 山东 潍坊 261000;2.山东大学附属千佛山医院神经内科, 山东 济南 250014;3.山东大学附属千佛山医院医学研究中心, 山东 济南 250014
  • 收稿日期:2015-12-22 出版日期:2016-04-10 发布日期:2016-04-10
  • 通讯作者: 李秀华. E-mail:lxh731023@126.com E-mail:lxh731023@126.com
  • 基金资助:
    山东省优秀中青年科学家科研奖励基金(2008BS03012);首都医科大学神经生物国家重点实验室开放课题(3500-112291)

Neuroprotective effect of adenovirus-mediated GDNF gene in mice models of Parkinsons disease

WANG Si1,2, LI Xiuhua2, DU Juan3, YUE Longtao3, WANG Yao3, LIU Fei2, GUO Pei1,2   

  1. 1. Weifang Medical University, Weifang 261000, Shandong, China;
    2. Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
    3. Central Laboratory, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2015-12-22 Online:2016-04-10 Published:2016-04-10

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摘要： 目的 探讨腺病毒介导的神经胶质细胞源性神经营养因子(GDNF)基因脑内转移对帕金森病(PD)的保护作用。 方法 采用C57Bl/6小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-henyl-l,2,3,6-tetrahydropyridine, MPTP)法建立PD模型,随机分为重组GDNF腺病毒(Ad-GDNF)实验组和对照组。Ad-GDNF实验组将Ad-GDNF定向注射至侧脑室,对照组将无GDNF基因的腺病毒定向注射至侧脑室,并测量体质量,进行行为学实验评分,行中脑黑质酪氨酸羟化酶(TH)免疫组化染色,高压液相色谱-电化学仪(HPLC-ECD)检测纹状体多巴胺(DA)、5-羟色胺(5-HT)及5-羟吲哚乙酸(5-HIAA)含量,采用ELISA、RT-PCR法检测Ad-GDNF在中脑的表达。 结果 侧脑室注射病毒后2周,Ad-GDNF实验组体质量、行为学实验得分、黑质酪氨酸羟化酶(TH)阳性细胞、纹状体DA含量均显著高于对照组(P<0.05);Ad-GDNF实验组在中脑内有过表达,中脑GDNF含量约是对照组2倍。 结论 侧脑室注射腺病毒介导的GDNF基因可减轻1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-henyl-l,2,3,6-tetrahydropyridine, MPTP)诱发的小鼠DA能神经元进行性变性,保护DA能神经元,提示这一手段在PD保护性治疗方面具有一定的应用价值。

关键词: 6-四氢吡啶, 神经胶质细胞源性神经营养因子, 腺病毒, 帕金森病, 基因治疗, 3, 1-甲基-4-苯基-1, 2

Abstract: Objective To investigate the neuroprotective effect of adenovirus-mediated glial cell line-derived neurotrophic factor(GDNF)gene intracerebrally transferred on the treatment of Parkinsons disease(PD). Methods PD models were established by intraperitoneal injection of 1-methyl-4-henyl-l,2,3,6-tetrahydropyridine(MPTP)［30 mg/(kg·d)in C57Bl/6 mice. The models were then divided into Ad-GDNF experimental group and control group. Ad-GDNF was injected into the lateral ventricle of mice in the experimental group. Negative virus was injected into the lateral ventricle of mice in the control group. The body weight of all mice was measured. The neuroprotective effect of Ad-GDNF was evaluated with behavioral tests, immune histochemical assay of the tyrosine hydroxylase(TH)-positive neurons in the substance nigra and measurement of monoamine level in the striatum. The expression of the exogenous GDNF gene in the brain was detected with ELISA and RT-PCR. Results Compared with control group, the experimental group showed improved motor functions(P<0.01)and less loss of body weight(P<0.05), better survival of TH-positive cells(P<0.05), higher DA levels(P<0.05)after two weeks of intracerebroventricular injection. The exogenous 山 东 大 学 学 报 (医 学 版)54卷4期 -王思,等.侧脑室注射腺病毒介导的GDNF基因对帕金森病的保护作用 \=-GDNF gene was efficiently over expressed in the experimental group. GDNF protein level in midbrain of the experimental group was twice of the control group. Conclusion Intracerebroventricular injection of adenovirus mediated GDNF gene significantly can protect the dopaminergic neurons of nigrostriatal system from MPTP-induced injury and is conducive in the treatment of Parkinsons disease.

Key words: Glial cell line-derived neurotrophic factor, Adenovirus, Parkinsons disease, Gene therapy, 1-methyl-4-henyl-l,2,3,6-tetrahydropyridine

中图分类号: 

  • R741.02
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