中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (6): 865-874.doi: 10.4103/1673-5374.208540

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

免疫调节剂和微小RNA可作为缺血性卒中的神经恢复疗法

  

  • 收稿日期:2017-05-08 出版日期:2017-06-15 发布日期:2017-06-15

Immunomodulators and microRNAs as neurorestorative therapy for ischemic stroke

Bridget Martinez1, Philip V. Peplow2   

  1. 1 Department of Molecular and Cellular Biology, University of California, Merced, CA, USA; 2 Department of Anatomy, University of Otago, Dunedin, New Zealand
  • Received:2017-05-08 Online:2017-06-15 Published:2017-06-15
  • Contact: Philip V. Peplow,phil.peplow@otago.ac.nz.

摘要:

大多数脑卒中是由于血管闭塞导致缺血,并且包括两种主要类型,即血栓形成和栓塞。炎症和免疫反应在缺血性卒中的结果中起重要作用。具有免疫调节特性的药物和基于细胞的疗法可有益于治疗缺血性卒中。通过免疫调节治疗引起的微小RNA的可能变化可能是至关重要的。文中描述的药物研究已经鉴定了与mRNA靶标失调相关的几种差异调节miRNA,或者几种神经保护基因的上调,从而突出了特异性miRNA如miR-762,-1892,-200a,-145的潜在神经保护作用。MiR-124,-711,-145是预测能够介导抗炎通路和小胶质细胞/巨噬细胞M2样活化表型相关miRNA。文中审查的基于细胞的治疗研究主要使用间充质干细胞或人脐带血细胞,并显示了其改善脑卒中动物的功能和神经学结果。MiR-145和miR-133b涉及神经细胞重塑和脑卒中后的功能恢复。人脐带血细胞可以降低促炎因子,促进脑卒中糖尿病动物的M2巨噬细胞极化。

Abstract:

Most of all strokes are ischemic due to occlusion of a vessel, and comprise two main types, thrombotic and embolic. Inflammation and immune response play an important role in the outcome of ischemic stroke. Pharmaceutical and cell-based therapies with immunomodulatory properties could be of benefit in treating ischemic stroke. Possible changes in microRNAs brought about by immunomodulatory treatments may be important. The pharmaceutical studies described in this review have identified several differentially regulated miRNAs associated with disregulation of mRNA targets or the upregulation of several neuroprotective genes, thereby highlighting the potential neuroprotective roles of specific miRNAs such as miR-762, -1892, -200a, -145. MiR-124, -711, -145 are the strongly associated miRNAs predicted to mediate anti-inflammatory pathways and microglia/macrophage M2-like activation phenotype. The cell-based therapy studies reviewed have mainly utilized mesenchymal stem cells or human umbilical cord blood cells and shown to improve functional and neurological outcomes in stroke animals. MiR-145 and miR-133b were implicated in nerve cell remodeling and functional recovery after stroke. Human umbilical cord blood cells decreased proinflammatory factors and promoted M2 macrophage polarization in stroke diabetic animals.

Key words: ischemic stroke, immunomodulators, pharmaceutical therapies, cell-based therapies, microRNAs, animal models