胚鼠腹侧中脑和胚肾联合移植治疗Parkinson病的实验研究

为了提高移植多巴胺(DA)能神经元的存活率和促进神经元生长,将胚鼠腹侧中脑和胚肾联合移植入Parkinson病(PD)模型大鼠脑内,检测胚肾对移植DA能神经元的影响。先用神经毒剂6 OHDA损毁大鼠左侧中脑被盖腹侧区和黑质致密部建立PD动物模型,再将胚脑的腹侧中脑(A组)、胚脑的腹侧中脑和胚肾(B组)分别移植入左侧纹状体尾壳核,C组为空白对照。于移植后3d、1月、3月将动物处死,采用酪氨酸羟化酶(TH)免疫组化法观察3组动物移植部位DA能神经元的存活和生长状况。在移植部位可见B组较A组的TH阳性神经元和纤维的数量明显增多,C组的移植部位未见TH阳性神经元和纤维;A、B两组的移植针道及其周围也有TH阳性神经元和纤维;B组的TH阳性神经元数量、体积和神经纤维的密度均大于A组。移植1个月和3个月后,A、B两组大鼠的旋转行为均较C组减少(P<0. 05)。以上结果提示胚肾具有良好的神经营养作用,能促进移植DA能神经元的存活和生长。

FETAL VENTRAL MESENCEPHALON AND KIDNEY CO-TRANSPLANTATION INCREASES GRAFTED DOPAMINE NEURONS SURVIVAL AND IMPROVES BEHAVIORAL RECOVERY IN HEMI-PARKINSONIAN RATS

Recent studies have demonstrated that both developing and adult kidneys express many kinds of neurotrophic factors. In the present study, whether fetal kidney transplantation could be beneficial for dopaminergic neuron survival and their neurite growth transplanted from the fetal ventral mesencephalon into the striatum was investigated. A lesion of dopaminergic neurons was performed in adult SD rats by injecting 6-hydroxydopamine (6-OHDA) into the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Four weeks after the lesion, 36 rats were selected and divided into three groups: A group (fetal ventral mesencephalon graft group), B group (fetal ventral mesencephalon-fetal kidney co-graft group), C group (control group). Three days, one month, three months after grafting, the rats were sacrificed and used for tyrosine hydroxylase (TH) immunohistochemical staining. The fetal kidney transplantation increased the survival of dopaminergic neurons. There was a significant improvement in apomorphine-induced rotation with both single fetal ventral mesencephalon graft and fetal ventral mesencephalon-kidney co-graft. TH immunohistochemistry revealed a significantly denser innervation of the host striatum from the fetal ventral mesencephalon-kidney co-graft than that from the single fetal ventral mesencephalon graft. TH immunoreactive positive neurons were also significantly increased in the co-graft transplanted group compared with the single fetal ventral mesencephalon graft (P <0.05). The present results suggest that fetal kidney could excrete neurotrophic factors which might increase the survival of transplanted dopaminergic neurons and their neurite growth.