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Mechanism of Yishen Huoxue Tongqiao Formula in Improving Unilateral Vestibular Labyrinth Destruction by Regulating Metabolism-neuroplasticity

  • role： First author第一作者
  • Affiliation：

    The First Clinical College of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

  • Email：ty97214@163.com
  • Introduction：田雨，在读博士，从事眩晕及耳蜗微循环障碍的基础与临床研究，E-mail：ty97214@163.com
TIAN Yu1,  
  • role： Corresponding author通信作者
  • Affiliation：

    Affiliated Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

  • Email：lengh1976@163.com
  • Introduction：冷辉，博士，主任医师，博士生导师，从事眩晕及耳蜗微循环障碍的基础与临床研究，E-mail：lengh1976@163.com； *
LENG Hui2*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Affiliated Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

  • Email：qrp36707@163.com
  • Introduction：曲汝鹏，博士，主任医师，从事眩晕及耳蜗微循环障碍的基础与临床研究，E-mail：qrp36707@163.com
QU Rupeng2*,  
  • Affiliation：

    The First Clinical College of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

HAO Xianglong1,  
  • Affiliation：

    Affiliated Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

WANG Aiping2,  
  • Affiliation：

    Affiliated Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

SHI Lei2,  
  • Affiliation：

    Affiliated Hospital of Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

QU Zhongyuan2,  
  • Affiliation：

    Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

DONG Ye3,  
  • Affiliation：

    Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

MA Xiande3,  
  • Affiliation：

    Liaoning University of Traditional Chinese Medicine，Shenyang 110000，China

HUANG Yangling3

resumen

ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）.Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg-1）， and betahistine group （1.62 mg·kg-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43.ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）.ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

palabra clave

Yishen Huoxue Tongqiao Formula;medial vestibular nucleus;dendritic spine;neuron;Nissl staining

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