摘要
以6-羟多巴胺单侧损毁大鼠中脑多巴胺能系统,建立帕金森病动物模型,通过检测给予阿普吗啡后大鼠的旋转圈数,判断多巴胺的减少或恢复程度。向脑内植入能表达酪氨酸羟化酶的遗传工程改造细胞,以改善大鼠模型的运动失常和纹状体多巴胺水平。将带有酪氨酸羟化酶基因的重组载体pCMVTH在体外通过脂质体转染技术转入成肌细胞和肌管细胞内,再将这些经遗传改造、表达酪氨酸羟化酶的细胞植入纹状体。结果显示,这些表达酪氨酸羟化酶的肌细胞可在大鼠模型体内长期存活,并使模型大鼠的异常运动明显改善及使纹状体内多巴胺水平升高,显示此种方法有很重要的临床实用性。
The rats with an unilateral 6 OHDA induced lesion of the dopamic system in the midbrain were provided as animal models for parkinson disease (PD). The quantifiable rotation of those rats after apomorphine administration and their striatal levels of dopamine (DA) and its major metabolities were used for exploring the degree of DA loss or replacement. In order to induce significant improvement of motor abnomalities and striatal DA levels in rat model, the present study was carried out by intracerebral grafting of the genetically modifed cells which could express tyrosine hydroxylase (TH). The recombinant vectors, a plasmid of pCMVTH containing TH gene, were transferred into the cultured myoblasts and myotubes ex vivo by using lipofection technique. The genetically altered cells expressing TH in vitro were then grafted into the striatum of PD rat models. The results showed that those TH expressing muscle cells had a long term survival in vivo and induced a marked decrease in abnormal locomotion finor rat models. This indicates that the strategy for gene therapy presented by present study might be clinical useful.
出处
《解剖学报》
CAS
CSCD
北大核心
1997年第2期127-131,共5页
Acta Anatomica Sinica
基金
国家自然科学基金
北京市自然科学基金
北京市科委资助