过表达SDF-1a帕金森病小鼠模型的建立与评价

Establishment and Evaluation of the SDF-1a Over-Expressing Mouse Model of Parkinson Disease

目的:探讨建立及评价稳定的脑内过表达基质细胞衍生因子-1a(stromal cell derived factor-1,SDF-1a)的帕金森病(Parkinson's disease,PD)小鼠模型的方法。方法:采用间隔多次注射方法将小剂量1-甲基-4-苯基-1,2,3,6四氢吡啶(1-methyl-4-phenyl-tet-rahy dropyridine,MPTP)注射已立体定向下脑内注射质粒pDsRed2-N1-SDF-1a的小鼠皮下,在不同时间点观察小鼠的行为改变,以及检测小鼠爬杆时间、脑内酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞数量以及多巴胺含量(dopamine,DA)含量的变化,同时观察和检测小鼠脑内SDF-1a的表达。结果:MPTP组小鼠出现PD样行为表现,并至少持续40d;各检测时间点下,MPTP组小鼠的爬杆时间显著长于对照组,而TH阳性细胞数量及DA含量较对照组显著减少;同时,在MPTP组小鼠脑内可观察质粒红色荧光蛋白的表达,以及可以检测到SDF-1a蛋白的表达。结论:采用立体定向质粒注射及间隔多次小剂量皮下注射MPTP的方法能够有效建立了过表达SDF-1a帕金森病小鼠模型,为进一步观察SDF-1a趋化细胞迁移并治疗PD的研究提供了前提条件。

Objective To establish and evaluate a stromal cell derived factor - 1 a （SDF - la） mouse Par- kinson disease （PD） model. Methods Low - dose 1 - methyl -4 - phenyl - tet - rally dropyridine （MPTP） was subcutaneously injected at different time points into mice which had been intracerebrally treated with pD- sRed2＇-＇N1 -SDF- la. And behaviors were observed at different time points, cerebral DA levels assayed by high performance liquid chromatography （HPLC）, TH positive ceils counted in SN and SDF - 1 a determined in the brain. Results PD - like behaviors were observed in the mice of M-PTP group and could last for at least 40 days. At different time points, the pod -grabbing time in MPTP group was longer than that in control group, but the TH positive cells and DA content were markedly tecreased when compared with control group.lii .addition, plasmid＂ transcription was noted in MPTP group and SDF - 1 a expression was detectable. Conclu- sion Intermittent arid multiple subcutaneous injections of MPTP can be used to establish a PD model in SDF - 1 a over - expressing mice, which provides an experimental basis for the investigation of the role of SDF - 1 a induced chemo taxis and migration in the treatment of PD.