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磁共振波谱观察骨髓间充质干细胞移植治疗帕金森病大鼠纹状体神经代谢物的变化

Neural metabolite changes in corpus striatum after rat multipotent mesenchymal stem cells transplanted in hemiparkinsonian rats by magnetic resonance spectroscopy.

机构信息

1Department of Histology and Embryology, Weifang Medical University , Weifang, Shandong , PR China.

出版信息

Int J Neurosci. 2013 Dec;123(12):883-91. doi: 10.3109/00207454.2013.814132. Epub 2013 Aug 1.

Abstract

OBJECTIVE

To investigate the biochemical changes in striatum after rat bone marrow mesenchymal stem cells (MSCs) were transplanted into hemiparkinsonian rats and to further confirm the therapeutic effects of rat MSCs for Parkinson's disease (PD).

METHODS

5-bromo-2-deoxyuridine (BrdU)-labeled MSCs were transplanted into the corpus striatum of the 6-hydroxydopamine (6-OHDA)-injected side of six PD model rats. Before and 8 weeks after MSC transplantation, ethological changes in PD rats were assessed. The expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum were measured using immunohistochemical methods. The differentiation of MSCs was detected by double immunofluorescence techniques. The concentrations of neural metabolites of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were measured by ¹H-magnetic resonance spectroscopy (MRS). Relative concentrations of NAA/Cr and Cho/Cr were calculated.

RESULTS

The behavior of PD rats in rotarod tests improved, and there were statistical differences in TH-positive cells in SN and TH-positive terminals in striatum after the transplantation of BrdU-labeled MSCs. Transplanted MSCs differentiated into MAP-2-positive neurons. Especially compared with pre-MSC transplantation, the neural metabolite NAA/Cr ratio of the 6-OHDA-injected side of the striatum increased (P < 0.05) and the Cho/Cr ratio decreased (P < 0.05).

CONCLUSION

MSCs transplantation apparently improves neuronal function in the striatum of PD rats.

摘要

目的

观察骨髓间充质干细胞(MSCs)移植入偏侧帕金森病(PD)大鼠纹状体后纹状体的生化变化,进一步证实大鼠 MSCs 对 PD 的治疗作用。

方法

将 BrdU 标记的 MSCs 移植入 6-羟多巴胺(6-OHDA)单侧损毁 PD 模型大鼠纹状体。MSCs 移植前及移植后 8 周,采用行为学方法观察 PD 大鼠的行为学变化;免疫组织化学方法检测黑质(SN)和纹状体酪氨酸羟化酶(TH)的表达;双免疫荧光技术检测 MSCs 的分化;氢质子磁共振波谱(1H-MRS)检测纹状体 N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)等神经代谢物的浓度,计算 NAA/Cr 和 Cho/Cr 的相对浓度。

结果

PD 大鼠在旋转棒实验中的行为得到改善,SN 中 TH 阳性细胞和纹状体中 TH 阳性终末的数量在 MSCs 移植后均有统计学差异。移植的 MSCs 分化为 MAP-2 阳性神经元。与 MSC 移植前相比,6-OHDA 注射侧纹状体的神经代谢物 NAA/Cr 比值增加(P<0.05),Cho/Cr 比值降低(P<0.05)。

结论

MSCs 移植明显改善 PD 大鼠纹状体神经元功能。

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