Mechanism of Xixintang in Protecting Blood-brain Barrier in Alzheimer's Disease Model Rats Based on AQP4 Polarization
10.13422/j.cnki.syfjx.20251809
- VernacularTitle:基于AQP4极化探讨洗心汤对阿尔茨海默病模型大鼠血脑屏障的保护机制
- Author:
Siyuan JIA
1
;
Yongchang DIWU
2
;
Yuan TIAN
1
;
Jie GAO
1
;
Meirong WU
1
;
Dengkun WANG
3
Author Information
1. Shaanxi University of Chinese Medicine，Xianyang 712046，China
2. College of Basic Medicine，Shaanxi University of Chinese Medicine，Xianyang 712046，China
3. Affiliated Hospital of Shaanxi University of Chinese Medicine，Xianyang 712046，China
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
blood-brain barrier;
amyloid-β1-42 （Aβ1-42）;
aquaporin-4 （AQP4）;
Xixin decoction
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(9):1-10
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis paper aims to investigate the effects of Xixintang on aquaporin-4 （AQP4） polarity distribution， blood-brain barrier （BBB） function， and neuroinflammationin rats with Alzheimer's disease （AD）， thereby revealing the potential mechanism through which this formula protects the BBB by regulating AQP4 polarization. The aim is to provide a scientific basis for clinical treatment. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， a probiotic group， a donepezil group， and an Xixintang group. The model was established by intraperitoneal injection of D-galactose （D-Gal） combined with bilateral intracerebroventricular injection of amyloid-β25-35 （Aβ25-35）. The probiotic group （30.85 mg·kg-1）， donepezil group （0.88 mg·kg-1）， and Xixintang group （1.174 g·kg-1） received daily gavage administration， while the normal and model groups received intragastric administration with an equal volume of normal saline for one month. Cognitive ability was assessed by using the Morris water maze. BBB permeability was detected via Evans blue extravasation. The contents of interleukin-6 （IL-6）， amyloid-β1-42 （Aβ1-42）， and tumor necrosis factor-α （TNF-α） in the hippocampal tissues were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of zonula occludens-1 （ZO-1）， occludin， tissue inhibitor of metalloproteinase-1 （TIMP-1）， matrix metalloproteinase-9 （MMP-9）， and AQP4 in the hippocampal tissues were detected by western blot. The expression and co-localization levels of Aβ1-42， ionized calcium-binding adapter molecule 1 （IBA1）， and AQP4/platelet endothelial cell adhesion molecule 31 （CD31） in the hippocampal region were examined by immunofluorescence. ResultsCompared with the normal group， the model group exhibited a significant decline in cognitive ability （P<0.01） and a marked increase in Evans blue extravasation in the brain （P<0.01）. The expressions of ZO-1， occludin， and TIMP-1 were significantly decreased （P<0.01）， while the expressions of AQP4 and MMP-9 were significantly increased （P<0.01）. The co-localization level of AQP4/CD31 was significantly reduced （P<0.01）， and the expressions of Aβ1-42， IL-6， TNF-α， and IBA1 were significantly elevated （P<0.01）. Compared with the model group， the Xixintang group showed significant improvement in cognitive ability （P<0.01） and a significant reduction in Evans blue extravasation in the brain （P<0.01）. The expressions of occludin， TIMP-1， and ZO-1 were significantly increased （P<0.05， P<0.01）， while the expressions of AQP4 and MMP-9 were significantly decreased （P<0.05）. The co-localization level of AQP4/CD31 was significantly enhanced （P<0.01）， and the expressions of Aβ1-42， IL-6， TNF-α， and IBA1 were significantly reduced （P<0.05， P<0.01）. ConclusionXixintang may improve cognitive function and alleviate AD pathology in AD model rats by regulating AQP4 polarity distribution， thereby breaking the vicious cycle of "Aβ deposition-neuroinflammation-BBB damage" and restoring the homeostasis of the microenvironment in the brain.
