Mechanisms of Tianma Goutengyin in Alleviating Neuronal Injury in Vascular Dementia Model Rats by Inhibiting A1 Astrocyte Activation via Regulating TNF-α/STAT3/α1ACT Signaling Pathway
10.13422/j.cnki.syfjx.20251539
- VernacularTitle:天麻钩藤饮通过调节TNF-α/STAT3/α1ACT信号通路抑制A1型星型胶质细胞激活减轻血管性痴呆模型大鼠神经元损伤作用机制
- Author:
Xiaoyan WANG
1
;
Min ZHAO
1
;
Feng TIAN
2
;
Min XIAO
3
;
Nan QU
1
;
Fugui LIU
1
;
Chixiao LIU
1
Author Information
1. The First Affiliated Hospital of Henan University of Chinese Medicine， Zhengzhou 450000， China
2. School of Medicine，Henan University of Chinese Medicine，Zhengzhou 450000，China
3. Experimental Animal Center，Hubei University of Chinese Medicine，Wuhan 430065，Chinaa
- Publication Type:Journal Article
- Keywords:
Tianma Goutengyin;
vascular dementia;
astrocytes;
tumor necrosis factor-α （TNF-α）/signal transducer and activator of transcription 3 （STAT3）/α1-antichymotrypsin C-terminal tail （α1ACT） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(7):56-65
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α （TNF-α）/signal transducer and activator of transcription 3 （STAT3）/α1-antichymotrypsin C-terminal tail fragment （α1ACT） signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups （n=12 per group）： Sham-operated group， model group， Tianma Goutengyin high-， medium-， and low-dose groups （5.13， 10.26， and 20.52 g·kg-1）， and a nimodipine group （8.1 mg·kg-1）. The vascular dementia model was established by permanent bilateral common carotid artery occlusion， followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test， and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 （IL-6） and C-C motif chemokine ligand 2 （CCL2） in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal neuronal morphology was observed by Nissl staining， and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and myelin basic protein （MBP）. Western blot analysis was performed to measure the protein expression levels of TNF-α， TNF receptor 1 （TNFR1）， phosphorylated STAT3 （p-STAT3）， α1ACT， IL-6， complement component 3 （C3）， BDNF， S100 calcium-binding protein A10 （S100A10）， and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group， the model group showed a significantly reduced relative recognition index in the novel object recognition test （P<0.01）， prolonged immobility time and increased immobility frequency in the forced swimming test （P<0.01）. Hippocampal IL-6 and CCL2 levels were significantly increased （P<0.01）. Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies （P<0.01）. MBP-positive expression was significantly decreased （P<0.01）， apoptosis was significantly increased （P<0.01）， BDNF-positive expression was significantly reduced （P<0.05）， and GFAP-positive expression was significantly increased （P<0.01）. In addition， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly elevated （P<0.01）， while BDNF and S100A10 expression levels were significantly decreased （P<0.01）. Compared with the model group， all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index （P<0.05）， shortened immobility time and reduced immobility frequency （P<0.05， P<0.01）. IL-6 and CCL2 levels were significantly decreased （P<0.01）， neuronal number was significantly increased （P<0.05， P<0.01）， and MBP-positive expression was significantly enhanced （P<0.01）. Apoptosis was significantly reduced （P<0.01）， BDNF-positive expression was significantly increased （P<0.05）， and GFAP-positive expression was significantly decreased （P<0.01）. Moreover， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly decreased （P<0.01）， while BDNF and S100A10 protein expression levels were significantly increased （P<0.01）. ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway， thereby reducing neuronal apoptosis and improving learning and memory function.
