Establishment and evaluation of a disease-syndrome combined rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome
10.3969/j.issn.1005-4847.2025.08.001
- VernacularTitle:慢性脑缺血气虚血瘀证病证结合大鼠模型的建立与评价
- Author:
Zhuoxiu LIU
1
;
Yangjing HAO
;
Hao FU
;
Qinqing LI
;
Jianjun ZHANG
;
Shifeng CHU
;
Zhao ZHANG
;
Zhuoqing CAO
;
Wenbin HE
Author Information
1. 山西中医药大学,中医脑病学山西省重点实验室,太原 030024
- Publication Type:Journal Article
- Keywords:
chronic cerebral ischemia;
Qi deficiency and blood stasis syndrome;
disease-syndrome combination;
sleep deprivation;
animal model
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(8):1091-1104
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.
