损毁帕金森病大鼠腹侧苍白球对纹状体内谷氨酸含量影响.doc

损毁帕金森病大鼠腹侧苍白球对纹状体内谷氨酸含量影响 　 作者：曾水林，李涛，杨鹏，康学军，萧静，黄晓，刘俊华 【关键词】 帕金森病 Content changes of glutamic acid in striatum induced by lesion of ventral pallidum in rats with Parkinsons disease 　　【Abstract】 AIM: To observe the content changes of glutamic acid (Glu) in the striatum after lesion of ventral pallidum (VP) in Parkinsons disease (PD) rats. METHODS: The model of PD was made by injecting 6hydroxydopamine (6OHDA) into the left substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) of the rats. After damaging VP of the PD rats, we observed the changes of rotation behavior and detected the content of Glu in striatum by high pressure liquid chromatography (HPLC) with fluorescence detection analysis. RESULTS: After lesion of VP, the rotating behavior decreased markedly, and the content of Glu in striatum (μg/g) (3.0±0.4) was higher than that in normal (2.2±0.7), model (1.3±0.2) and sham groups (1.4±0.4)（Plt;0.05）. It reached the peak at 2nd week then subsided, but still higher than that in other groups. CONCLUSION: Lesion of VP can block the release of Glu or check its combination with its receptors, thus reducing the neural toxicity of Glu. These effects may be beneficial for the treatment of PD. 　　【Keywords】 Parkinsons disease; ventral pallidum; glutamic acid; rats 　　【摘要】 目的： 观察腹侧苍白球(VP)损毁后帕金森病(PD)大鼠纹状体内谷氨酸(Glu)含量的变化. 方法： 应用6羟基多巴胺(6OHDA)制备偏侧PD大鼠模型，插入电极直流电毁损VP，观察毁损后PD大鼠的旋转行为，应用高效液相色谱检测纹状体内Glu的含量. 结果： VP损毁术后PD大鼠偏侧旋转行为明显改善,纹状体内Glu的含量(μg/g) (3.0±0.4)比正常对照组(2.2±0.7) 、模型对照组(1.3±0.2)和假手术组(1.4±0.4)都要高（Plt;0.05），在术后第2周时达高峰，以后逐渐下降，但仍高于其他三组. 结论： VP毁损可能会减少Glu的释放或与其受体的结合，从而对神经元的毒性作用减弱，有助于PD症状的改善. 　　【关键词】　帕金森病；腹侧苍白球；谷氨酸；大鼠 　　0引言 　　帕金森病(Parkinsons disease, PD)是中老年中枢神经系统的退行性变疾病. 用微电极导向核团毁损术治疗PD，具有显著改善其症状、损伤小、副作用少等优点，因而对于用药物难以控制的中晚期PD患者，这种方法已成为首选的治疗手段. 近年来的研究表明，兴奋性通路对控制PD运动症状起关键性的作用. 本实验我们探讨直流电毁损腹侧苍白球(ventral pallidum, VP) 治疗PD的效果及作用机制，为临床应用核团毁损术治疗PD提供理论依据. 　　1材料和方法 　　1.1材料 　　健康SD大鼠60只，雌雄不拘，体质量200~300 g. 用4 g/L戊巴比妥钠40 mg/kg腹腔注射麻醉，固定于江湾Ⅱ型脑立体定位仪，根据Paxinos等［1］脑立体定向图谱，按照文献［2］