X盒结合蛋白1转染神经干细胞移植帕金森大鼠黑质中相关递质及核蛋白的表达

Effects of X binding protein-1 gene-modified neural stem cells transplantation on expression of related neurotransmitters and nucleoprotein in the substantia nigra of rat Parkinson's disease model

背景:既往研究发现,X盒结合蛋白1基因可以转染至神经干细胞中并稳定过表达X盒结合蛋白1,转染后的神经干细胞移植对脑梗死的治疗作用优于普通神经干细胞。目的:通过测定转染后神经干细胞移植对帕金森大鼠模型黑质内单胺类递质和α-突触核蛋白水平的影响,研究转染后的神经干细胞移植对帕金森病的治疗作用。方法:将27只帕金森病大鼠随机数字表法均分为3组。对照组侧脑室内移植PBS,神经干细胞组移植空白神经干细胞悬液,转染组移植X盒结合蛋白1基因修饰神经干细胞悬液。分别于移植后7,14,21,28d对各组大鼠进行诱导旋转实验观察神经功能;Westernblot检测α-突触核蛋白水平;黑质切片后免疫组化染色测酪氨酸羟化酶(+)神经细胞。结果与结论:转染组大鼠黑质内α-突触核蛋白表达量降低,酪氨酸羟化酶(+)神经细胞数高于神经干细胞组和对照组,且大鼠旋转实验中旋转行为改善。表明在帕金森病中,X盒结合蛋白1转染的神经干细胞分化为多巴胺能神经元的分化率高,转染后可降低α-突触核蛋白的聚集,从而改善帕金森症状起到治疗目的。

BACKGROUND： Previous studies have shown that X binding protein-1 gene can be transfected into the neural stem cells and is steadily expressed. X binding protein-1 gene transfected neural stem cells transplantation for cerebral infarction treatment is better than ordinary neural stem cells. OBJECTIVE： To study the treatment effect of X binding protein-1 transfected neural stem cells transplantation on Parkinson＇s disease through detecting the influence on monoamine neurotransmitters and （1-synuclein levels in the substantia nigra of rat Parkinson＇s disease model. METHODS： Twenty-seven rat Parkinson＇s disease models were divided into three groups randomly, and 9 rats in each group. The rats in control group were transplanted with PBS through the lateral ventricle, while neural stem cells group was transplanted with blank neural stem cell suspension, and transfection group was transplanted with X binding protein-1 gene-modified neural stem cells. In 7, 14, 21 and 28 days after transplantation, neurobehavioral score of the rats was estimated respectively, α-synuclein level was examined by Western blot, and the tyrosine hydroxylase positive cells were revealed by immunohistochemical staining. RESULTS AND CONCLUSION： The expression of α-synuclein was decreased in the transfection group. The number of tyrosine hydroxylase positive cells in the transfection group was higher than that in the neural stem cells group and control group, and the rotation speed of transfection group was decreased obviously. The results show that the differentiation rate of binding protein-1 gene-modified neural stern cells differentiating into dopaminergic neurons is higher and the transfection can reduce α-synuclein content in rat substantia nigra, so as to treat Parkinson＇s symptoms