损毁或高频刺激丘脑底核对黑质神经元的保护作用

目的：探讨损毁或高频刺激丘脑底核（STN）对帕金森病（PD）大鼠黑质致密部神经元的保护作用及其可能的发生机制。方法：应用每羟基多巴胺（6-OHDA）制备偏侧PD大鼠模型,于丘脑底核（STN）区分别植入刺激电极给以高频电刺激,或注入鹅膏蕈氨酸（IA）进行损毁后,观察PD大鼠行为改变;运用尼氏（Nissl）染色、DNA原位末端标记技术（TUNEL）、免疫组化方法检测并分析黑质致密部（SNc）神经元存活及凋亡发生情况。结果：刺激组黑质致密部凋亡神经元的阳性率显著低于模型组与损毁组（P〈0．05）。与正常大鼠相比,刺激组Bel-2染色呈强阳性,Bel-2／Bax比值较高,模型组、损毁组SNc区的Bcl-2表达有所下调,Bax表达增加,Bcl-2／Bax比值降低（P〈0．05）,虽然损毁组SNc的凋亡阳性神经元少于模型组（P〈0．05）,但二者的Bel-2、Bax的表达及Bel-2／Bax比值无显著性差异（P〉0．05）。结论：损毁或高频刺激SIN对PD大鼠黑质SNc神经元存在保护作用,高频刺激的长期保护作用更为明显。

The neuroprotective effects of lesion and high frequency stimulation of the subthalamic nucleus on the substantia nigra neurons

Aim： To investigate the neumpmtective effects of lesion and high frequency stimulation（HFS） of the subthalamic nucleus（STN） on the substantia nigra pars compacta（SNc） neurons and its probable mechanism. Methods： The PD models were induced by unilateral administration of 6-bydroxydopamine into right substantia nigra in mrs. After the high-frequence stimulation to STN and injection of ibotenic acid to STN on PD rats, the changes of behavior were observed. The substantia nigra neurons were detected by using special-dyeing, TUNEL techniques and immunohistochemistry methods. Results： In the stimulation group, the apoptotic rate was significantly lower than PD modal group and lesion group（ P 〈 0.05）. Compared with normal rats, model group and lesion one had the similar results of expression of Bcl-2, Bax and their ratio, which were lower expression of Bcl-2, higher expression of Bax and the decrease of their ratio（ P 〈 0.05）. In the stimulation group, the expression of Bcl-2 and Bcl-2/Bax were much higher than model group and lesion group. The number of apoptotic neurons of rats in lesion group was smaller than model ones（ P 〈 0.05）, but there was no significant difference in expression of Bcl-2, Bax and their ratio（ P 〉 0.05）. Conclusion： Lesion or HFS of STN have the neuroprotective effects on SNc neurons of PD rats, and HFS has a better long-term effect.