中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 112-119.doi: 10.4103/1673-5374.264470

• 原著:退行性病与再生 • 上一篇    下一篇

神经干细胞移植治疗帕金森病:趋化因子受体4/基质细胞衍生因子1轴参与的作用

  


  • 出版日期:2020-01-15 发布日期:2020-05-20
  • 基金资助:

    国家自然科学基金项目(81241126,81360197);昆明医科大学科技处项目(2013C227);昆明医科大学科技联合特别基金(2014FB041)

Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Jiao-Tian Xu1, Yuan Qian2, Wei Wang1, 3, Xiao-Xiang Chen1, Yang Li1, Yu Li1, Zhi-Yong Yang1, Xiao-Bin Song1, Di Lu4, Xing-Li Deng1   

  1. 1 Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
    2 Diagnosis Prenatal Unit, Department of Obstetrics, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
    3 The People’s Hospital of Chuxiong Yi Autonomous Prefecture, Chuxiong, Yunnan Province, China
    4 Rehabilitation Engineering Research Laboratory, Biomedicine Engineering Research Center, Kunming Medical University, Kunming, Yunnan Province, China
  • Online:2020-01-15 Published:2020-05-20
  • Contact: Xing-Li Deng, MD,dxlkmmu@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81241126 (to XLD) and 81360197 (to XLD);
    a grant from the Department of Science and Technology of Kunming Medical University in China, No. 2013C227 (to XLD); the Joint Special Fund for the Department of Science and Technology of Kunming Medical University in China, No. 2014FB041 (to XBS).

摘要:

既往研究显示神经干细胞移植具有治疗帕金森病的潜力,但其具体作用机制仍然不清楚。由于基质细胞衍生因子1及其受体趋化因子受体4是细胞迁移的重要调节因子,因而作者推测趋化因子受体4/基质细胞衍生因子1轴可能参与神经干细胞移植治疗帕金森病的过程。为此,实验构建了右侧上行黑质纹状体多巴胺能通路注射6-羟基多巴胺的帕金森病模型大鼠,然后以于右侧黑质注射5 𝜇L神经干细胞悬液(1.5 × 10/L)进行治疗,并设立大鼠于移植后连续3d,1次/d腹腔注射趋化因子受体4拮抗剂AMD3100 1.25 mL/kg,观察对神经干细胞移植的变化情况。(1)实验以阿扑吗啡诱导旋转检测大鼠的帕金森样行为,以免疫荧光染色检测脑组织酪氨酸羟化酶、趋化因子受体4和基质细胞衍生因子1的免疫阳性反应,以实时定量PCR分析右侧黑质中基质细胞衍生因子1及趋化因子受体4mRNA的表达水平,以Western blot分析脑组织中基质细胞衍生因子1及趋化因子受体4的表达水平。(2)实验结果见神经干细胞移植能显著减少阿扑吗啡诱导的旋转,增加右侧黑质中基质细胞衍生因子1及趋化因子受体4mRNA及蛋白的表达,增强脑组织中脑组织酪氨酸羟化酶、趋化因子受体4和基质细胞衍生因子1的免疫阳性反应,而注射AMD则会抑制上述效果。实验说明趋化因子受体4/基质细胞衍生因子1轴可能在神经干细胞移植治疗帕金森病中发挥重要作用。动物实验方案于2014年4月1日经昆明医科大学动物护理与使用委员会批准,批准号SYXKK2015-0002。

orcid: 0000-0002-7456-9051 (Xing-Li Deng)

关键词: 帕金森病, 神经干细胞, 趋化因子受体4, 基质细胞衍生因子1, AMD3100, 黑质, 纹状体, 神经再生

Abstract:

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease, but its specific mechanism of action is still unclear. Stromal cell-derived factor-1 and its receptor, chemokine receptor 4 (CXCR4), are important regulators of cell migration. We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease. A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway, and then treated with 5 μL of neural stem cell suspension (1.5 × 104/L) in the right substantia nigra. Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation. Parkinson-like behavior in rats was detected using apomorphine-induced rotation. Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase, CXCR4, and stromal cell-derived factor-1 in the brain. Using quantitative real-time polymerase chain reaction, the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured. In addition, western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4. Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation, increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra, and enhanced the immunoreactivity of tyrosine hydroxylase, CXCR4, and stromal cell-derived factor-1 in the brain. Injection of AMD3100 inhibited the aforementioned effects. These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease. This study was approved by the Animal Care and Use Committee of Kunming Medical University, China (approval No. SYXKK2015-0002) on April 1, 2014.

Key words: AMD3100, corpus striatum, CXCR4, neural stem cells, Parkinson’s disease, stromal cell-derived factor-1, substantia nigra