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目的探讨血管内皮生长因子(VEGF)基因转移对帕金森病(PD)大鼠的保护作用。方法携带VEGF165基因的腺病毒(Ad-VEGF165)感染PD模型大鼠纹状体后,采用大鼠旋转行为观察、免疫组织化学方法和高效液相色谱技术检测VEGF165基因转移的PD大鼠行为学变化、黑质纹状体酪氨酸羟化酶(TH)、层黏蛋白(laminin)和胶质纤维原性酸性蛋白(GFAP)的表达以及纹状体区多巴胺(DA)及代谢产物含量变化。并与重组腺病毒载体(Ad-Lacz)组及磷酸盐缓冲液(PBS)组进行比较。结果Ad-VEGF165成功感染PD大鼠并高表达目的基因和蛋白。感染Ad-VEGF165的大鼠获得行为学改善,其黑质和纹状体TH阳性细胞数和纤维密度与对侧半球的比值(0．42±0．11和0．56±0．10)高于Ad-LacZ组(0．20±0．10和0．28±0．09)和PBS组(0．22±0．13和0．24±0．08),P<0．01;纹状体区血管和胶质细胞数量均明显增多;Ad-VEGF165感染组大鼠纹状体区DA及代谢产物含量与对侧比值也高于对照组。结论Ad-VEGF基因转移能保护PD大鼠多巴胺能神经元,血管和胶质细胞的增生可能参与了VEGF对在体多巴胺能神经细胞的保护机制。
Objective To investigate the protective effect of vascular endothelial growth factor (VEGF) gene transfer on Parkinson’s disease (PD) rats. Methods The adenovirus carrying VEGF165 (Ad-VEGF165) was used to infect the striatum of rat model of PD. The behavior of PD rats with VEGF165 gene transfer was examined by immunohistochemistry and high performance liquid chromatography , Tyrosine hydroxylase (TH), laminin, and glial fibrillary acidic protein (GFAP) in striatum and the content of dopamine (DA) and metabolites in striatum. And compared with the recombinant adenovirus vector (Ad-Lacz) group and the phosphate buffered saline (PBS) group. Results Ad-VEGF165 successfully infected PD rats and high expression of the target gene and protein. The behavioral improvement was obtained in rats infected with Ad-VEGF165 with a significantly higher ratio of TH positive cells and fiber density to contralateral hemispheres (0.42 ± 0.11 and 0.56 ± 0.10) in substantia nigra and striatum In the Ad-LacZ group (0.20 ± 0.10 and 0.28 ± 0.09) and the PBS group (0.22 ± 0.13 and 0.24 ± 0.08), P <0.01; The amount of vascular and glial cells in the area of striatum were significantly increased. The content of DA and metabolites in the striatum of Ad-VEGF165 infected group were also higher than those in the control group. Conclusion Ad-VEGF gene transfer can protect PD rats from dopaminergic neurons, vascular and glial cells proliferation may be involved in the protective effect of VEGF on dopaminergic neurons in vivo.