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Recombinant adenovirus carrying glial cell line-derived neurotrophic factor gene protect midbrain dopaminergic neurons in mice
Author(s): 
Pages: 256-260
Year: Issue:  3
Journal: JOURNAL OF PEKING UNIVERSITY(HEALTH SCIENCES)

Keyword:  帕金森病胶质细胞源性神经营养因子重组腺病毒多巴胺MPTP;
Abstract: 目的:观察携带大鼠来源的胶质细胞源性神经营养因子(rGDNF)的重组腺病毒在小鼠帕金森模型中有无保护中脑多巴胺(DA)能神经元对抗神经毒素甲基-苯基-四氢吡啶(MPTP)损伤的作用.方法:将LacZ重组腺病毒(Ad-LacZ)通过脑立体定位仪注入小鼠单侧纹状体,分别于注射后24 h、72 h、10 d和30 d灌流取脑做X-Gal染色,观察报告基因在小鼠脑内的表达情况;将rGDNF重组腺病毒(Ad-rGDNF)通过脑立体定位仪注入小鼠单侧纹状体.两者均于72 h后给予MPTP损伤中脑DA能神经元,1 周后用高压液相色谱分析纹状体中DA、3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的含量.结果:Ad-LacZ注射后24 h表达较弱,72 h逐渐增强,10 d仍可见到较强表达,30 d则逐渐减弱.LacZ基因的表达范围比较局限,胶质细胞和神经元都能被感染,并且未见明显的腺病毒载体引起的细胞毒性作用.注射Ad-rGDNF侧纹状体DA含量较MPTP损伤组和MPTP+Ad-LacZ组显著升高, 而未注射侧无明显升高.此外,DA主要代谢产物DOPAC和HVA的含量也明显升高,而DOPAC/DA、HVA/DA比值则明显降低.结论:Ad-rGDNF能显著保护中脑DA能神经元对抗MPTP的损伤.
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