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目的 观察不同损毁程度的帕金森病 (PD)小鼠模型纹状体多巴胺D2 受体 (DR)功能变化 ,探讨12 5I IBZMD2 R功能显像的临床意义。方法 根据注射MPTP(30 0mg·kg-1·d-1)天数的不同将小鼠分为MPTP1,3,5和 7d模型组和对照组 ,静脉注射12 5I IBZM 2 0 μCi,1h后行放射自显影。高效液相色谱 电化学法 (HPLC ECD)检测纹状体多巴胺 (DA)及其代谢产物浓度。免疫组化酪氨酸羟化酶 (TH)染色观察黑质和纹状体的病理改变。结果 与对照组比较 ,MPTP损毁 1,3,5d组的纹状体 /皮层感兴趣区放射活性比值分别增高 8% ,16 %和 17% ,而MPTP损毁 7d组与对照组无明显差异。MPTP损毁各组的纹状体DA浓度分别降低 47% ,75 % ,95 %和 95 %。TH染色可见黑质TH阳性神经元随MPTP损毁加重而数量减少。结论 MPTP损毁的PD小鼠模型纹状体D2 R功能在损毁程度轻时逐渐增强 ,呈上调现象 ;而在损毁程度严重时则降至正常。表明在PD早期宜使用DR激动剂。在体动态监测纹状体的D2 R功能状态有助于了解在疾病的不同阶段PD患者对多巴制剂及DR激动剂的治疗反应性。
Objective To observe the changes of dopamine D2 receptor (DR) function in striatum of Parkinson’s disease (PD) mice with different degrees of damage, and to explore the clinical significance of 125I IBZMD2R functional imaging. Methods According to the different days of injection of MPTP (30 0 mg · kg-1 · d-1), mice were divided into MPTP1, 3, 5 and 7d model group and control group, 125I IBZM 20 μCi intravenously, Self-development. High performance liquid chromatography (HPLC) electrochemical detection of dopamine (DA) and its metabolite concentration in striatum. Immunohistochemical tyrosine hydroxylase (TH) staining was used to observe the pathological changes of substantia nigra and striatum. Results Compared with the control group, the ratios of radioactivity in the striatum / cortex of interest area increased by 8%, 16% and 17% respectively in the 1, 3 and 5 days MPTP group, while no significant difference was found between the MPTP group and the control group. The concentration of striatal DA in each group decreased by 47%, 75%, 95% and 95%, respectively, for MPTP lesions. TH staining showed that substantia nigra TH-positive neurons decreased with MPTP damage. Conclusions The D2R function of striatum in MPTP-lesioned PD mice gradually increases and increases when the degree of lesion is mild. However, the function of D2R decreases to normal in severe damage. This suggests that DR agonists should be used early in PD. Dynamic monitoring of striatal D2R status in vivo helps to understand the therapeutic responsiveness of PD patients to dopa and DR agonists at various stages of the disease.