Effect of electroacupuncture on vascular remodeling in rats with cerebral ischemia by regulating irisin based on VEGF/Akt/eNOS signaling pathway

IF 3.5 3区医学 Q2 NEUROSCIENCES Brain Research Bulletin Pub Date : 2025-02-01 DOI:10.1016/j.brainresbull.2025.111192

Lu Cao , Wenchao Ding , Yashuo Feng , Chong Guan , Li Liu , Hongyu Xie , Kewei Yu , Dongyan Xu , Lijuan Zhao , Xuan Sha , Xiaoman Deng , Santian Wu , Yangrui Wang , Yi Wu , Tingting Zhang , Nianhong Wang

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Abstract

Objective

This study aimed to explore the cumulative effects and expression patterns of electroacupuncture (EA) on irisin secretion, observe the effects of EA on the recovery of neurobehavioral function and vascular remodeling after cerebral ischemia, and elucidate the mechanism by which EA promotes vascular remodeling by regulating irisin expression.

Methods

A rat model of left middle cerebral artery occlusion (MCAO) was prepared, and EA was performed. Tissue distribution and expression of irisin were determined by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Type III fibronectin domain protein 5-silenced adeno-associated virus (rAAV-shFNDC5) was injected into the lateral ventricle as a control. Neurobehavioral function was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and behavioral experiments, while vascular remodeling was evaluated using laser speckle blood flow imaging, and the expressions of irisin and vascular remodeling-related factors were measured by ELISA and Western blotting.

Results

The number of FNDC5-positive neurons, fluorescence intensity, and irisin expression reached their maximum increase after 7 days of EA treatment. In addition, the EA group exhibited a significant reduction in cerebral infarct volume and impairment of neurobehavioral function, an increase in cerebral blood flow and microvascular diameter on the ischemic side, and significantly higher expression levels of FNDC5, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS). However, rAAV-shFNDC5 significantly weakened the therapeutic effects of EA.

Conclusions

EA upregulated irisin expression, reaching a peak after 7 days of EA and then stabilizing. EA facilitated vascular remodeling after cerebral ischemia, and this might be associated with the activation of the irisin-mediated VEGF/Akt/eNOS signaling pathway.

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电针基于VEGF/Akt/eNOS信号通路调控鸢尾素对脑缺血大鼠血管重构的影响

目的：探讨电针（EA）对鸢尾素分泌的累积效应及表达规律，观察电针对脑缺血后神经行为功能恢复及血管重构的影响，阐明电针通过调节鸢尾素表达促进血管重构的机制。方法：制备大鼠左大脑中动脉闭塞（MCAO）模型，并进行电镜观察。采用免疫荧光法、酶联免疫吸附法（ELISA）和Western blotting检测鸢尾素的组织分布和表达。将III型纤维连接蛋白结构域5沉默腺相关病毒（rAAV-shFNDC5）注射到侧脑室作为对照。采用2,3,5-三苯四唑氯（TTC）染色和行为学实验评价大鼠神经行为功能，采用激光散斑血流显像评价大鼠血管重构，采用ELISA和Western blotting检测鸢尾素及血管重构相关因子的表达。结果：EA处理7天后，fndc5阳性神经元数量、荧光强度、鸢尾素表达均达到最大。此外，EA组脑梗死面积和神经行为功能损伤显著减少，缺血侧脑血流量和微血管直径增加，FNDC5、脑源性神经营养因子（BDNF）、血管内皮生长因子（VEGF）、蛋白激酶B （Akt）和内皮型一氧化氮合酶（eNOS）表达水平显著升高。而rAAV-shFNDC5明显减弱了EA的治疗效果。结论：EA可上调鸢尾素的表达，在EA作用7天后达到峰值，随后趋于稳定。EA促进脑缺血后血管重构，这可能与鸢尾素介导的VEGF/Akt/eNOS信号通路的激活有关。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.