帕金森病大鼠模型的骨髓间充质干细胞移植疗效的磁共振波谱探讨

Evaluation of the Therapeutic Effect of Mesenchymal Stem Cell Transplantation Using 1.5T MRS in Rat Model of Parkinson's Disease

目的 利用1.5T质子磁共振波谱(1H-MRS)监测活体帕金森病大鼠模型骨髓间充质干细胞(mesenchymal stem cells ,MSCs)移植治疗前后纹状体区的神经代谢变化,以探讨1.5T磁共振波谱分析在评价MSCs移植术疗效中的应用价值.方法 30只正常大鼠,以6-羟基多巴胺(6-OHDA)单侧(右侧)损毁制备偏侧帕金森病模型.在活体状态下,分别于造模后3周、MSCs移植后4周及8周应用Philips1.5T临床型磁共振仪扫描,对双侧纹状体区进行1H-MRS采集,分析该区N-乙酰天门冬氨酸/肌酸(NAA/Cr)、胆碱/肌酸(Cho/Cr)比值变化,同时对大鼠进行行为学检测.利用黑质酪氨酸羟化酶免疫组织化学染色对黑质致密部(SNc)神经元进行定量分析.结果 MSCs移植后8周组(C组)大鼠损毁侧(右侧)NAA/Cr比值与未处理组(A组)和MSCs移植后4周组(B组)相比明显升高(P<0.05);B,C组损毁侧Cho/Cr比值较A组明显降低(P<0.05),且分别明显低于其对侧(P均<0.05).B,C组旋转圈数分别较A组低(P均<0.05);C组旋转圈数较B组显著降低(P<0.05).三组损毁侧SNc TH阳性细胞生存率无显著差异(P均>0.05)..结论 1.5T磁共振波谱可以作为一种活体无创性检测方法,对帕金森病大鼠模型纹状体区MSCs细胞移植疗效进行动态监测而作出有价值的评价.

Objective Using 1.5 T proton magnetic resonance spectroscopy(~1H-MRS) in vivo to monitor the metabolic changes of the nerves in the striatum of Parkinson's disease(PD) rat before and after mesenchymal stem cells(MSCs) transplantation,so as to explore the value of 1.5T MR spectral analysis in evaluating the therapeutic effects of MSCs transplantation.Methods Parkinson's disease models with unilateral symptom were established by taking 6-hydroxydopamine(6-OHDA) to enforce unilateral(right) lesion in 30 normal rats.~1H-MRS was performed in vivo using Philips 1.5T clinical MR machine three weeks after lesion establishment,four weeks and eight weeks after MSCs transplantation separately and to analyze the changes of NAA/Cr,Cho/Cr ratio in the bilateral striatum.Meanwhile,the rats rotational behavior were also detected.PD rats'neurons in the substantia nigra were quantitatively analyzed by tyrosine hydroxylase immunohistochemical staining after the rats were sacrificeed.Results In eight weeks after MSCs transplantation group(C),NAA/Cr ratio of the damage side (right) increased significantly,compared with the untreated group(A) and four weeks after MSCs transplantation group(B);in the damage side of group B and group C,Cho/Cr ratio was significantly lower than that of group A and it was lower than that of opposite side.Rat's rotational behavior in group B and group C significantly reduced compared with group A;Rotational behavior in group C reduced than that of group B(P<0.05).The survival rate of TH-positive cells in the damage side striatum of three groups were no significant difference(P>0.05). Conclusion As a kind of non-invasive detection method in vivo,1.5T ~1H-MRS can be used to monitor the striatum of PD rat model dynamicly after MSCs transplantation,which could valuate the therapeutic effects efficiently.