摘要
目的探讨人胶质细胞源性神经营养因子(GDNF)基因治疗在肌萎缩性脊髓侧索硬化症(ALS)中的作用。方法 ALS小鼠随机分成AdCMVlacz对照组和AdCMVgdnf治疗组各12只。第9周肌肉注射AdCMVgdnf或AdCMVlacz病毒。第10周测试运动能力,并记录发病时间和生存时间。利用ELISA和免疫组织化学检测骨骼肌肉和脊髓中GDNF的表达,对脊髓运动神经元细胞数目和腓肠肌质量变化进行定量分析。结果①AdCMVgdnf治疗组ALS小鼠注射部位肌肉中GDNF水平为(6 589.0±325.0)pg/mg,而对照组为(75.3±18.9)pg/mg,治疗组高于对照组近100倍(P<0.01)。②对照组的腓肠肌质量为(88.6±14.5)mg,治疗组为(174.9±18.7)mg,差异有统计学意义(P<0.01)。③治疗组脊髓运动神经元细胞中GDNF较对照组明显增加,并且神经元细胞数目也明显增加(P<0.01)。④与对照组的发病时间(96.2±5.8)d比较,治疗组为(123.0±6.9)d,差异有统计学意义(P<0.01)。与对照组生存期(127.3±4.6)d比较,治疗组为(155.2±4.1)d,差异有统计学意义(P<0.01)。结论 AdCMVgdnf基因治疗对ALS小鼠脊髓运动神经元有保护作用,缓解肌肉萎缩,改善神经运动功能,延缓疾病的发生和延长生存期。
Objective To investigate the therapeutic effects of the human glial cell line-derived neurotrophic factor（GDNF） gene in a mouse model of amyotrophic lateral sclerosis（ALS）.Methods ALS mice with the SOD1G93A mutation were randomly divided into an AdCMVlacz control group and an AdCMVgdnf treatment group（each of 12 mice）.ALS mice were given AdCMVgdnf by intramuscular injection at 9 weeks of age.Motor strength and coordination were evaluated with the Rotarod test,beginning at 10 weeks of age.The time of disease onset and the longevity of the mice were recorded.Expression of GDNF in muscle and spinal cord at 16 weeks of age were detected by ELISA and immuno histochemical staining.The spinal cord motor neurons and skeletal muscles were also quantitatively analyzed. Results ①The level of GDNF expression in injected muscle was（6589.0±325.0）pg/mg in the treatment group,which was about 100 times more than in the control group（75.3±18.9） pg/mg（P0.01）.② The weight of the gastrocnemius was（88.6±14.5） mg in control group,and（174.9±18.7）mg in the treatment group,the difference being significant （P0.01）.③ In the spinal cord,both the GDNF level and the motor neuron number in the treatment group were higher than in the control group（P0.01）.④ Disease onset was delayed（123.0±6.9） days of age in the treatment group as compared with（96.2±5.8）days in the control group（P0.01）.The mice′s longevity in the treatment group was（155.2±4.1） days as compared with（127.3±4.6） days in the control group（P0.01）. Conclusions Gene therapy for ALS model mice using AdCMVgdnf resulted in neuroprotective effects on spinal motor neurons,and significant improvement in skeletal muscle atrophy and neurological movement.Disease onset was delayed and longevity was prolonged.
出处
《山东大学学报（医学版）》
CAS
北大核心
2011年第11期25-29,共5页
Journal of Shandong University:Health Sciences
基金
国家自然科学基金资助课题(30872658
30400460)
山东省自然科学杰出青年基金资助课题(JQ200808)
山东省优秀中青年科学家奖励基金(2007BS3045)
作者简介
张文华（1970-），男，副教授，主要从事脑肿瘤、神经变性疾病和脑血管病治疗及发病机制研究。E-mail：wzhang215@hotmail．com
