帕金森病大鼠黑质细胞凋亡与Bax蛋白表达相关性的实验研究

Experimental Study on the Relationship Between Substantia Nigral Apoptosis and Expression of Bax Protein in Rats with Parkinson Disease

目的:观察6-羟基多巴胺(6-OHDA)能否诱发黑质细胞凋亡以及Bax蛋白表达与黑质细胞凋亡的关系。方法:72只Wistar雄性大鼠随机分为对照组36只及通过脑立体定位注射6-0HDA的方法建立的大鼠帕金森病模型组(PD)组36只,采用TUNEL方法、免疫组织化学、电镜等观察术后l、7、l4及2ld时2组大鼠脑黑质细胞凋亡的数量及超微结构变化,并检测黑质细胞Bax蛋白的表达。结果:术后TUNEL法发现,与对照组比较,PD组存在明显的黑质细胞凋亡(P<0.05),且在1-21d时细胞凋亡数逐渐增高;电镜观察显示,PD组黑质细胞存在典型细胞凋亡,Bax蛋白表达在ld为最高,其后很快下降,但仍显著高于对照组。结论:6-羟基多巴胺能诱发大鼠黑质细胞凋亡,Bax蛋白是黑质细胞凋亡的关键启动因素。

Objective.. To study the induction of apoptosis of substantia nigra by 60HDA evoke and the relation ship between substantia nigral apoptosis and expression of Bax protein. Methods.. Seventy-two Wistar male rats were randomly divided into control group （36） and Parklnson disease model group （PD group, 36）. Using （TUNEL） method , in situ hibridization and electron microscopic techniques, the number of nigral apoptosis and the changes of ultrastructure were observed 1, 7, 14, 21 days after stereotaxic injection of 60HDA into right side of the mesencephic ventral tegmental area （VTA） and substantia nigra pars compacta （SNc） of rats. The expression of Bax protein was detected. Results： The number of substantia nigral apoptosis in the PD group was much more than that in the control group, and from 1st to 21st day the number of substantia nigral apoptosis was increased gradualy. In the PD group the ultrastructure of substan tia nigra exhibited morphological characteristics of apoptosis. The expression of Bax protein attained the peak value promptly at 1st day, and then decreased gradually. Bax protein in the PD group was higher than in the control group. Conclusion： Apoptosis of substantia nigra can be induced by 60HDA. Apoptosis of substantia nigral induced by 6-OH- DA contributes to the pathogenesis of PD. As a key evoking factor, Bax protein involves in pathogenesis of PD.