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异丙酚对MPTP损伤的小鼠黑质多巴胺神经元的保护作用

Protection of the mouse nigrostriatal dopaminergic system by propofol pretreatment against a MPTP lesion in vivo
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摘要 目的 观察异丙酚对 1 甲基 4 苯基 1,2 ,3 ,6 四氢吡啶 (1 methyl 4 phenyl 1,2 ,3 ,6 tetrahydropyridineMPTP)损伤的小鼠纹状体多巴胺神经元的影响以及可能的作用机制。方法 给予Propofol 10 0mg/ (kg·d)后注射MPTP 2 0mg/ (kg·d) ,用药 6d。 12d后分离纹状体应用高效液相 -电化学方法检测纹状体多巴胺、二羟基苯乙酸及高香草酸的含量水平 ,应用12 5I- β-CIT放射性配基和免疫组化的方法检测多巴胺转运蛋白的活性和黑质神经元的损伤情况。结果 异丙酚可增加MPTP模型鼠多巴胺及其代谢产物的含量 ,异丙酚处理组DA ,DOPAC ,HVA的含量分别为 (8.2 417± 1.692 ) μg/ g、(1.3 81± 0 .486) μg/g和 (1.63 3 9± 0 .5 73 ) μg/ g ,与MPTP损伤组比较 ,明显增加。异丙酚亦可抑制黑质酪氨酸羟化酶 (TH)阳性神经元的减少。MPTP组注射MPTP 6d后 ,纹状体DAT为 (5 .3 13± 0 .64 2 )与正常组 (6.992± 0 .5 48) μg/ g比较显著下降 (P <0 .0 1) ,P +M组纹状体DAT为 (6.5 65± 0 .40 5 ) ,明显高于MPTP组 (P <0 .0 1) ,即减轻纹状体内多巴胺转运蛋白密度下降。结论 异丙酚对MPTP损伤的DA神经元具有一定的保护作用 。 Objective To investigate the protection of propofol treatment against a MPTP lesion in mice. Methods Mice were successively pretreated with propofol 100 mg/(kg·d) before a MPTP 20 mg/(kg·d) administration for 6 days. At 12th day after drug pretreatment, the levels of dopamine, 3,4-dihydroxynylacetic acid and homovanillic acid were measured by HPLC with electrochemical detection, the density of dopamine transporters and tyrosine hydroxyl activity were examined using 125 I-β-CIT as a tracer and immunohistochemical studies, respectively. Results The value of dopamine (8.241 7±1.692)μg/g, 3,4-dihydroxynylacetic acid (1 381±0.486)μg/gand homovanillic acid (1.633 9±0.573)μg/g in propofol group were increased compared with control group. The number of tyrosine hydroxyls positive neurons after propofol pretreatment was significantly increased compared with a single MPTP administration. The density of dopamine transporters was significantly increased (6.565±0.405) compared with MPTP group(5.313±0.642) (P<0.01). Conclusion These results suggest that the pretreatment of propofol can confer protective effects to nigrostriatal dopaminergic system against a MPTP lesion.
出处 《山西医科大学学报》 CAS 2003年第2期119-121,共3页 Journal of Shanxi Medical University
关键词 神经毒素 1-甲基-4-苯基-1 2 3 6-四氢吡啶 异丙酚 多巴胺神经元 转运蛋白 MPTP损伤 propofol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurons mice
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