Investigation of sympathetic nerve in Parkinson's disease model mice

给C57BL6雄性小鼠(15周龄)注射MPTP，建立帕金森病模型。MPTP注射剂量为40 mg/bw。将小鼠分为6组(对照组、MPTP给药前1d、4d、7d、21d和3次[7、14、21d])。在RI实验中，注射~(125)I-MIBG 4h后处死小鼠，测定心脏摄取~(125)I-MIBG、去甲肾上腺素、多巴胺、甲状腺浓度。在非再灌流实验中，测定纹状体多巴胺浓度和心脏去甲肾上腺素转运体。I-MIBG摄取在1d内迅速下降，7d后逐渐恢复。MPTP重复给药3次后，上述指标均降低。纹状体多巴胺和心脏去甲肾上腺素浓度的变化规律相似。而心脏多巴胺和酪氨酸浓度无明显变化，说明去甲肾上腺素的合成损伤具有时间依赖性。去甲肾上腺素转运体结合电位在1d内迅速降低，此后无明显变化。在帕金森病模型小鼠的交感神经中，去甲肾上腺素转运体的结合电位和去甲肾上腺素的合成均在早期降低。但此后，去甲肾上腺素的合成逐渐恢复。而长期反复服用MPTP，更使去甲肾上腺素合成减少。

MPTP was injected to C57BL6 male mice (15 weeks) and Parkinson's disease model mice was made. Injected dose of MPTP was 40 mg/BW. Mice were divided into 6 groups (control, MPTP administration 1-day, 4-days, 7-days, 21-days and 3-times [7, 14, 21 days] before). In RI experiment, (14 mice in each group) 4 hours after ^<125>I-MIBG injection, mice were sacrificed, and cardiac ^<125>I-MIBG uptake, norephephrine, dopamine, thyrosine concentration were measured. In non-RI experiment (20 mice each), striatum dopamine concentration and cardiac norepinephrine transporter was measured. ^<125>I-MIBG uptake was rapidly reduced in 1-day, followed by gradually recovered in 7-day. And it was reduced after 3-times repeated MPTP administration. Striatum dopamine and cardiac norepinephrine concentration showed similar pattern. However, cardiac dopamine and tyrosine concentration showed no significant change, that means norepinephrine synthesis damage is time-dependent. Binding potential of norepinephrine transporter rapidly reduced in 1-day, however no significant change was found after that. In sympathetic nerve of Parkinson's disease model mice, both of binding potential of norepinephrine transporter and norepinephrine synthesis reduced in early stage at first. However, norepinephrine synthesis recovered gradually after that. And long-term and repeated MPTP administration, still more makes reduction of norepinephrine synthesis.