中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (4): 869-874.doi: 10.4103/1673-5374.353500

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

芬戈尔莫德减轻局灶性缺血再灌注损伤大鼠神经血管单元损伤

  

  • 出版日期:2023-04-15 发布日期:2022-10-29

Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury

Xiao-Yu Zhu1, Ting-Ting Ma2, Yang Li2, Ming-Qi Zhang2, Liang Zhao3, Jia Liang2, *, Lian-Qiu Min1, *   

  1. 1Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China;  2Institution of Life Science, Jinzhou Medical University, Jinzhou, Liaoning Province, China;  3School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • Online:2023-04-15 Published:2022-10-29
  • Contact: Lian-Qiu Min, MS, minlianqiu@163.com; Jia Liang, PhD, liangjia@jzmu.edu.cn.
  • Supported by:
    This work was supported by grants from the National Natural Science Foundation of China, No. 81971231 (to JL) and Liaoning Revitalization Talents Program, No. XLYC1907178 (to JL).

摘要:

最近,芬戈里莫德(FTY-720)--一种从冬虫夏草中分离出来的新开发的免疫抑制剂,表现出广泛的生物活性--在缺血性脑血管疾病中的作用引起了广泛关注。研究从神经血管单元角度评估了FTY-720对缺血再灌注损伤大鼠模型的作用及可能的作用机制。结果显示,芬戈莫德可(1)明显减少梗死体积,改善神经功能缺损程度,减轻血脑屏障渗漏;(2)通过降低脑微血管中两种重要的紧密连接蛋白(occludin and claudin-5)的降解及脑微血管中鞘氨醇-1-磷酸受体1蛋白水平, 修复脑微血管损伤;(3)降低脑内促炎因子白细胞介素17A蛋白水平,减轻脑内炎症反应;(3)减少神经元凋亡。这些结果表明,芬戈莫德对缺血性脑卒中后的神经血管和功能恢复方面有积极的作用。

https://orcid.org/0000-0003-4953-6239 (Lian-Qiu Min); 

https://orcid.org/0000-0001-7311-1260 (Jia Liang)

Abstract: Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms. Fingolimod (FTY-720) is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities, and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases. In the current research, the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model. Our results revealed that FTY-720 markedly decreased infarct volume, promoted neurological function recovery, and weakened the blood-brain barrier permeability of ischemic rats. The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels. These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

Key words: astrocyte, blood-brain barrier, claudin-5, FTY-720, interleukin-17A, ischemic stroke, neural protection, neurovascular unit, occludin,  , sphingosine-1-phosphate receptor 1