脑内移植NGF诱导的PC-12细胞治疗大鼠帕金森病的研究

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

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(pheochromocytoma cells,PC-12)移植入模型大鼠纹状体内,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(50μg/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.

Nerve growth factor （NGF）-induced PC-12 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. PC-12 cells were treated by N GF （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 PC-12 cells may be used transplantation treatment of the PD.