脑内移植NGF诱导的PC-12细胞治疗大鼠帕金森病的研究

实验利用SD大鼠复制6-羟多巴胺(6-hydroxydopamine,6-OHDA)完全损伤型帕金森动物模型,将神经生长因子(nerve growth factor,NGF)处理后的肾上腺嗜铬细胞瘤细胞(plleoclxromocytoma cells,PC-12)移植人模型大鼠纹状体内,观察模型动物行为改善和移植PC-12细胞的存活情况.经行为学检测,6-OHDA动物模型复制成功率达55.1%.免疫组织化学、蛋白印迹检测结果显示模型动物黑质多巴胺能神经元数目减少,黑质酪氨酸羟化酶含量降低证明模型动物稳定、可靠.PC-12细胞经NGF(50 μg/L)连续诱导7 d,细胞逐渐平展、细胞膜变皱褶等神经元形态学特征出现后,于纹状体内行细胞移植术,经阿普吗啡(apomorphine,APO)诱导旋转行为有明显改善,蛋白印迹检测也发现移植侧具有显著的酪氨酸羟化酶免疫阳性信号.因此,NGF诱导后的PC-12细胞可以作为治疗帕金森的一种细胞供体.

Treatment with the Transplantation of Induced PC-12 by NGF in Parkinsonian Rats

Nerve growth factor(NGF)-induced PC12 cells was engrafted into striatum of Parkinsonian rats that generated by 6-hydroxydopamine(6-OHDA).The improvement of rats behaviors and survival of PC-12 cells were investigated.Rats of Parkinson's disease model were generated by 6-hydroxydopamine treated.Immunohistochemical staining and western blot results showed that the number of dopamine neuron was reduced in these rats.Rotation was tested by apomorphine exhibited about 55.1 % animals were success.PC12 cells were treated by NGF(50 ng/mL) for 7 days,the morphological charges were observed:cells were smooth,appeared appurtenances,and stopped cell division,the characters of neuron were observed.To determine the role of transplantation of those cells in striatum of 6-OHDA lesion rats,apormorphine-induced rotation was detected.Only those animals showed a reduction in rotation behavior over 4 weeks PC-12 transplantation.Moreover,western blot result showed the TH less expresses in striatum of transplantation rats.These results provided the support that NGF induced PC12 cells may be used transplantation treatment of the PD.