The Effect of Modified Ditan Decoction （涤痰汤） on Cognitive Function and Resting-State Functional Magnetic Resonance Imaging of the Brain in Chronic Intermittent Hypoxia Model Rats
10.13288/j.11-2166/r.2025.01.012
- VernacularTitle:加味涤痰汤对慢性间歇低氧模型大鼠认知功能及大脑静息态功能磁共振成像的影响
- Author:
Naijie CHEN
1
;
Xiaoting WANG
2
;
Fengsheng XU
3
;
Shuanghong SHEN
1
;
Zuanfang LI
4
;
Qin CHEN
2
;
Jin CHEN
1
;
Runhua WU
1
Author Information
1. College of Integrative Medicine，Fujian University of Traditional Chinese Medicine，Fuzhou，350122
2. Clinical Skill Center， Fujian University of Traditional Chinese Medicine
3. Affiliated People's Hospital，Fujian University of Traditional Chinese Medicine
4. Science and Technology Innovation and Transformation Center，Fujian University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
chronic intermittent hypoxia;
obstructive sleep apnea-hypopnea syndrome;
cognitive function;
resting-state functional magnetic resonance imaging;
entorhinal cortex;
β-amyloid;
microglia;
modified Ditan Decoction （涤痰汤）
- From:
Journal of Traditional Chinese Medicine
2025;66(1):71-78
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of modified Ditan Decoction （涤痰汤） on chronic intermittent hypoxia cognitive function and the potential function mechanism. MethodsTwenty-four Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， and a modified Ditan Decoction group， with eight rats in each group. Rats in the modified Ditan Decoction group were administered the decoction by gavage at 14.8 ml/（kg·d）， while the normal group and the model group received the same dose of normal saline. Thirty minutes after daily gavage， the rats in all three groups were placed in an intermittent hypoxia chamber. The oxygen concentration for the model group and the modified Ditan Decoction group was adjusted daily for 8 hours using a computer program to establish the model， while the normal group was exposed to the same airflow rate of ambient air. The intervention was continued for 12 weeks to establish a chronic intermittent hypoxia rat model. The Y-maze test was used to evaluate spatial working memory in the rats. Resting-state functional magnetic resonance imaging （rs-fMRI） was performed to detect whole-brain regional homogeneity （ReHo） and seed-based functional connectivity （FC）. Brain regions showing significant differences in rs-fMRI were selected for further analysis. Immunofluorescence was used to detect β-amyloid （Aβ） deposition and the number of ionized calcium-binding adapter molecule 1 （IBA1）-positive microglial cells. Immunohistochemistry was employed to assess the expression of synaptophysin （SYP）， the excitatory synapse marker vesicular glutamate transporter 1 （Vglut1）， and the inhibitory synapse marker vesicular γ-aminobutyric acid transporter （VGAT）. ResultsCompared with the normal group， the model group showed a reduced spontaneous alternation rate in the Y-maze test. The smoothed Z-score standardized regional homogeneity （SzReHo） value in the left entorhinal cortex significantly increased， and the FC value from this seed point to the left basal forebrain significantly reduced. Additionally， the model group exhibited significantly higher Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， decreased expression of SYP， Vglut1， and VGAT， along with an increased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. Compared to the model group， the modified Ditan Decoction group demonstrated an increased spontaneous alternation rate， a significantly reduced SzReHo value in the left entorhinal cortex， and a significantly increased FC value from this region to the left basal forebrain. Furthermore， this group showed significantly lower Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， increased levels of SYP， Vglut1， and VGAT， and a decreased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. ConclusionModified Ditan Decoction can reconstruct the projection from the left basal forebrain to the entorhinal cortex in chronic intermittent hypoxia， thereby reducing Aβ aggregation and excessive microglial activation in the left entorhinal cortex. This process improves the excitation/inhibition imbalance caused by synaptic remodeling， ultimately enhancing cognitive function in rats of chronic intermittent hypoxia.
