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外源性TH基因在帕金森氏病鼠脑内的表达--行为和TH免疫组化的研究

蒋芝华, 倪紫美, 周长福, 曹蕾, 郑仲承, 刘新垣, 赵迎春, 陈生弟

中科院上海生理研究所.上海 200031；中科院上海生物化学研究所.上海 200031；上海第二医科大学附属瑞金医院神经内科.上海 200025

摘要

用成年大鼠75只,给右侧黑质区注射6-羟基多巴胺,损毁黑质多巴胺能神经元,制备偏侧帕金森氏病(PD)鼠模型。4wk后,注射阿朴吗啡诱发大鼠向左侧旋转。结果是：实验组的PD鼠,在移植后的12d内旋转数比移植前明显减少,到d15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6d和12d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18d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。

关键词： 糖异生; 基因治疗; 酪氨酸羟化酶; 大鼠

Expression of foreign tyrosine hydroxylase gene in the rat model of Parkinson^s disease

Jiang Zhihua, Ni Zimei, Zhou Changfu, Cao Lei, Zheng Zhoucheng, Liu Xinyuan, Zhao Yingchun, Chen Shengdi

Shanghai Institute of Physiology, Chinese Academy of Sciences. Shanghai 200031； China；Department of Neurology, Shanghai Rui-jin Hospital. Shanghai 200025

Abstract

A total of 75 adult rats were used to produce hemiparkinson^s disease (PD) model by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right substantial nigra. Four weeks following the lesions, rats were tested for apomorphine (APO) -induced asymmetric rotation. Only rats that showed more than seven turns per minute were selected as PD models for transplantation. A tyrosine hydroxylase expression plasmid (pSVK3-TH) mixed with lipofectin was transplanted into the right striatum of 15 PD rats. Another 20 PD rats transplanted either with lipofectin or with pSVK3-TH served as controls. Every three days following transplantation, the perforpance of asymmetric rotation were tested and stained with the TH-immunohistochemistry. Only the animals grafted with pSVK3-TH mixed with lipofectin were found to show the decreased rotational behavior and a few TH-positive cells in the right striatum at the postgraft day 3-12, but not day 18. The results indicate that there exists a correlation between amelioration of asymmetric rotation and the TH gene expression in the denervated striatum.

Key words: gluconeogenesis;Gene therapy;Tyrosine hydroxylase;Rat

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蒋芝华, 倪紫美, 周长福, 曹蕾, 郑仲承, 刘新垣, 赵迎春, 陈生弟. 外源性TH基因在帕金森氏病鼠脑内的表达--行为和TH免疫组化的研究[J]. 生理学报 1997; 49 (2): .

Jiang Zhihua, Ni Zimei, Zhou Changfu, Cao Lei, Zheng Zhoucheng, Liu Xinyuan, Zhao Yingchun, Chen Shengdi. Expression of foreign tyrosine hydroxylase gene in the rat model of Parkinson^s disease. Acta Physiol Sin 1997; 49 (2): (in Chinese with English abstract).