慢性帕金森病MPTP猴模型纹状体区质子磁共振波谱的动态研究

Dynamic study of ~1H-MRS in the striatum of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced monkeys of Parkinson’s disease

目的观察慢性帕金森病(PD)1甲基4苯基1,2,3,6四氢吡啶(MPTP)猴模型纹状体区质子磁共振波谱(1H MRS)的动态变化,探讨1H MRS在PD早期诊断研究中的价值。方法4只健康成年雄性猕猴,以MPTP(皮下注射,0.1mg·kg1·d1)制备慢性PD全身模型,造模前及其后6周内每周应用GESigna1.5T超导型NV/i磁共振扫描系统,行双侧纹状体区1H MRS采集,观察氮乙酰天门冬氨酸(NAA)、胆碱化合物(Cho)和肌酸及磷酸肌酸(Cr),采用随机软件FuncTool4.0对各代谢物含量行半定量分析,计算NAA/Cr和Cho/Cr的变化,并与行为学评分、MPTP累积剂量进行相关分析。结果4只猴经MPTP处理后均达到PD诊断标准,平均出现症状时间为(18.3±1.3)d,行为学评分稳定时间为(26.3±1.3)d,MPTP的累积用量为(17.78±0.27)mg。相同时间点双侧纹状体区NAA/Cr和Cho/Cr比较差异无统计学意义(P>0.05);使用MPTP后第1周至行为学评分稳定期间,NAA/Cr呈进行性下降,Cho/Cr呈进行性升高,行为学评分稳定后NAA/Cr和Cho/Cr趋于稳定;MPTP处理后第3周NAA/Cr和Cho/Cr与正常组比较差异有统计学意义(t=3.59,P<0.05;t=4.77,P<0.05);MPTP累计剂量与NAA/Cr的变化呈显著负相关(r=-0.970,P<0.05);与Cho/Cr的变化呈显著正相关(r=0.924,P<0.05)。结论1H MRS能够早期发现慢性PDMPTP猴模型纹状体?

Objective Using proton magnetic resonance spectroscopy ( 1H-MRS) in vivo to observe dynamic metabolic degenerative changes in the striatum of 1-methyl-4- phenyl-1,2,3,6- tetrahydropyridine(MPTP)-induced monkey model of Parkinson’s disease (PD), to study the value of 1H-MRS in diagnosis of early stage of PD. Methods Four adult healthy male monkeys were treated daily with MPTP hydrochloride (Sigma, St. Louis, MO, USA) 0.1 mg·kg -1 ·d -1 im. until they reached a state of stable parkinsonism. 1H-MRS were used to measure biochemical changes in the striatum during MPTP-induced neurodegenerative processes on based MRI scanning. The spectra correlated with nitrogen-acetyl aspartate (NAA), choline-containing compounds(Cho), creatine (Cr) and the data were analyzed using the FuncTool 4.0 software package. NAA/Cr, Cho/Cr ratio were calculated, and correlative studies between the cumulative dosage of MPTP and behavior assessment were conducted. Results Four monkeys all reached the diagnostic scale of PD, symptoms of motor abnormalities appeared on (18.3±1.3)d, until (26.3±1.3)d the symptoms achieved stable .The last cumulative dosage of MPTP was (17.78±0.27)mg. 1 H-MRS showed the NAA/Cr ratio and the Cho/Cr ratio of bilateral striatum were in no significant differences (P>0.05). During the dynamic course of MPTP treatment, the NAA/Cr ratio gradually decreased and the Cho/Cr ratio gradually increased, compared with the normal ratio before MPTP treatment respectively, and the significant differences appeared (t=3.59,P<0.05;t=4.77,P<0.05) at the third week after MPTP treatment. The cumulative dosages of MPTP were correlated with NAA/cr ratio negatively(r=-0.97,P>0.05)and with Cho/Cr ratio positively (r=0.92, P<0.05) Conclusions This present results indicates that 1H-MRS could provide biochemical and metabolic information sensitively on chronically MPTP-treated monkey model of PD in vivo reflecting the changes of MPTP neurodegenerative toxicity and could be used as a noninvasive effective method with the help of diagnosis and treatment evaluation of PD. positively(r=0.92, ovidebiochemicaland