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EXPRESSION OF FOREIGN TYROSINE HYDROXYLASE GENE IN THE RAT MODEL OF PARKINSON'S DISEASE
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- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 2
- DOI:
- 10.3321/j.issn:0371-0874.1997.02.004
- Key Word:
- 帕金森氏病;基因治疗;酪氨酸羟化酶;大鼠
Abstract： 用成年大鼠75只,给右侧黑质区注射6-羟基多巴胺(6-OHDA),损毁黑质多巴胺能神经元,制备偏侧帕金森氏病(PD)鼠模型.四周后,注射阿朴吗啡(APO)诱发大鼠向左侧旋转.旋转数为每分钟7次以上的35只PD鼠作实验用.其中实验组15只,对照组20只.向实验组PD鼠右侧纹状体多点植入含大鼠酪氨酸羟化酶cDNA(THcDNA)的真核表达载体pSVK3-TH和脂质体Lipofectin混合的基因转染复合体.对照组分2组,每组10只.一组PD鼠右侧纹状体只植入pSVK3-TH,另一组仅植入Lipofectin.所有实验动物在移植后的18 d内,每隔3 d注射APO诱发旋转.并与移植前作比较.结果是:实验组的PD鼠,在移植后的12 d内旋转数比移植前明显减少,到第15天后,旋转数接近移植前水平.经TH免疫组织化学检查,在移植后6 d和12 d的,右侧纹状体内有TH免疫阳性细胞.主要位于移植周围.移植后18 d的,未发现TH免疫阳性细胞.对照组的所有PD鼠,除其不对称旋转数与移植前比无变化外,在右侧纹状体内,也无TH阳性细胞.本研究首先证明了脂质体可介导TH基因进入PD鼠纹状体内的细胞并获得成功的表达,表达时程与功能变化时程相一致.该结果可能会为PD病人基因治疗的临床应用提供新的参考资料.
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