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电针与骨髓基质细胞移植联合治疗缺血性脑卒中的协同作用。

Synergistic effects of electroacupuncture and bone marrow stromal cells transplantation therapy in ischemic stroke.

机构信息

Department of Acupuncture and Massage, Hainan Medical University, Haikou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2023 Apr;27(8):3351-3362. doi: 10.26355/eurrev_202304_32106.

DOI:10.26355/eurrev_202304_32106
PMID:37140285
Abstract

OBJECTIVE

Animal studies and clinical trials demonstrated the effectiveness of a combination of transplanted bone marrow stromal cells (BMSC) and electroacupuncture (EA) treatment in improving neurological deficits. However, the ability of the BMSC-EA treatment to enhance brain repair processes or the neuronal plasticity of BMSC in ischemic stroke model is unclear. The purpose of this study was to investigate the neuroprotective effects and neuronal plasticity of BMSC transplantation combined with EA in ischemic stroke.

MATERIALS AND METHODS

A male Sprague-Dawley (SD) rat middle cerebral artery occlusion (MCAO) model was used. Intracerebral transplantation of BMSC, transfected with lentiviral vectors expressing green fluorescent protein (GFP), was performed using a stereotactic apparatus after modeling. MCAO rats were treated with BMSC injection alone or in combination with EA. After the treatment, proliferation and migration of BMSC were observed in different groups by fluorescence microscopy. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry were performed to examine changes in the levels of neuron-specific enolase (NSE) and nestin in the injured striatum.

RESULTS

Epifluorescence microscopy revealed that most BMSC in the cerebrum were lysed; few transplanted BMSC survived, and some living cells migrated to areas around the lesion site. NSE was overexpressed in the striatum of MCAO rats, illustrating the neurological deficits caused by cerebral ischemia-reperfusion. The combination of BMSC transplantation and EA attenuated the expression of NSE, indicating nerve injury repair. Although the qRT-PCR results showed that BMSC-EA treatment elevated nestin RNA expression, less robust responses were observed in other tests.

CONCLUSIONS

Our results show that the combination treatment significantly improved restoration of neurological deficits in the animal stroke model. However, further studies are required to see if EA could promote the rapid differentiation of BMSC into neural stem cells in the short term.

摘要

目的

动物研究和临床试验证明了骨髓基质细胞(BMSC)移植与电针(EA)联合治疗在改善神经功能缺损方面的有效性。然而,BMSC-EA 治疗增强缺血性中风模型中脑修复过程或 BMSC 神经元可塑性的能力尚不清楚。本研究旨在探讨 BMSC 移植联合 EA 对缺血性中风的神经保护作用及神经元可塑性的影响。

材料与方法

采用雄性 Sprague-Dawley(SD)大鼠大脑中动脉闭塞(MCAO)模型。造模后,使用立体定位仪进行脑内 BMSC 移植,转染表达绿色荧光蛋白(GFP)的慢病毒载体。MCAO 大鼠单独或联合 BMSC 注射进行 EA 治疗。治疗后,荧光显微镜观察不同组 BMSC 的增殖和迁移。采用实时定量 PCR(qRT-PCR)、Western blot 和免疫组织化学检测损伤纹状体中神经元特异性烯醇化酶(NSE)和巢蛋白水平的变化。

结果

荧光显微镜下观察到大脑中的大多数 BMSC 被溶解;存活的移植 BMSC 较少,一些存活细胞迁移到病变部位周围。MCAO 大鼠纹状体中 NSE 过度表达,说明脑缺血再灌注引起的神经功能缺损。BMSC 移植与 EA 联合治疗可减弱 NSE 的表达,提示神经损伤修复。尽管 qRT-PCR 结果显示 BMSC-EA 治疗可提高巢蛋白 RNA 表达,但在其他检测中反应较弱。

结论

本研究结果表明,联合治疗可显著改善动物中风模型中神经功能缺损的恢复。然而,需要进一步研究 EA 是否可以在短期内促进 BMSC 快速分化为神经干细胞。

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