摘要
为评价转鼠酪氨酸羟化酶（TH）基因的成肌细胞脑内移植对偏侧帕金森病（PD）大鼠模型纹状体区多巴胺及代谢产物含量的影响，应用6－羟多巴胺损毁SD大鼠单侧黑质制备偏侧帕金森病臣模型。模型稳定必个月后，移植转TH基因的成肌细胞（n＝24）或未转基国的成肌细胞（n＝10）于偏侧PD鼠损毁侧纹状体。移植治疗后6个月，用高效液相色谱电化学法（HPLC－ECD）检测偏侧PD鼠模型纹状体区多巴胺、3，4－二羟苯乙酸（DOPAC）以及高香草酸（HVA）含量。结果转TH基因成肌细胞植入组PD鼠纹状体区多巴胺及代谢产物含量明显增高（P＜0．01），其中多巴胺含量从治疗前平均39．20Pg／mg提高至治疗后的985．71Pg／mg，相当于正常侧纹状体的49．99％．对照组植入未转基因的成肌细胞后纹状体多巴胺及代谢产物含量无明显变化（P＞0．05）。可见转鼠TH基因的成肌细胞脑内移植能够部分改善偏侧PD鼠模型纹状体区多巴胺的缺乏，成肌细胞是PD基因治疗的合适靶细胞之一。
The effect of genetically modified myoblasts expressing tyrosine hydroxylase (TH) on thestriatal dopamine content in hemiparkinsonian rats was studied. A rat model of hemiparkinsonism was induced by the unilateral administration of 6-hydroxydopamine(6-OHDA) into the substantia nigra. The genetically modified myoblasts expressing TH were administered stereotaxically into the lesioned striatum.Dopamine (DA) and metabolic products in the striatum of hemiparkinsonian rats were determined by highPerformance liquid chromatography-electrical chemistry (HPLC-ECD)six month after grafting. The levels ofDA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the grafted striatum of hemiParkinsonian rats were increased significantly arter grafting of TH-expressed myoblasts(p<0'01 ). The genetically modified myoblasts expressing TH is a potential approach to the treatment of Parkinson disease.
基金
国家自然科学基金!No3947Q261
卫生部优秀青年人才专项基金!No94AQ24
上海市科委青年科技启明星后计划!No.94QMH1402
关键词
帕金森病
基因治疗
转基因
成肌细胞
多巴胺
Parkinson disease
gene therapy
genetically modified myoblast
dopamine HPLC-ECD
