The Effect of Modified <italic style="font-style: italic">Ditan Decoction</italic> （涤痰汤） on Cognitive Function and Resting-State Functional Magnetic Resonance Imaging of the Brain in Chronic Intermittent Hypoxia Model Rats

CHEN Naijie; WANG Xiaoting; XU Fengsheng; SHEN Shuanghong; LI Zuanfang; CHEN Qin; CHEN Jin; WU Runhua

doi:10.13288/j.11-2166/r.2025.01.012

您当前的位置：

首页 >

文章列表页 >

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

更新时间：2024-12-31

- 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
- Journal of Traditional Chinese Medicine Vol. 66, Issue 1, Pages: 71-78(2025)
- 作者机构：
  
  1.福建中医药大学中西医结合学院，福建省福州市闽侯上街邱阳路1号，350122
  2.福建中医药大学临床技能中心
  3.福建中医药大学附属人民医院
  4.福建中医药大学科技创新与转化中心
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.01.012
  CLC：
- Received：13 March 2024，
  
  Revised：2024-05-29，
  
  Published：02 January 2025
- 稿件说明：
移动端阅览
陈乃洁,王小婷,徐峰圣等.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[J].中医杂志,2025,66(01):71-78.

CHEN Naijie,WANG Xiaoting,XU Fengsheng,et al.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[J].Journal of Traditional Chinese Medicine,2025,66(01):71-78.
陈乃洁,王小婷,徐峰圣等.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[J].中医杂志,2025,66(01):71-78. DOI： 10.13288/j.11-2166/r.2025.01.012.

CHEN Naijie,WANG Xiaoting,XU Fengsheng,et al.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[J].Journal of Traditional Chinese Medicine,2025,66(01):71-78. DOI： 10.13288/j.11-2166/r.2025.01.012.

摘要

目的

探讨加味涤痰汤对慢性间歇低氧认知功能的影响及可能作用机制。

方法

24只SD大鼠随机分为正常组、模型组、加味涤痰汤组，每组8只。加味涤痰汤组大鼠予加味涤痰汤14.8 ml/（kg·d）灌胃，正常组及模型组予相同剂量生理盐水灌胃。每日灌胃后30 min将3组大鼠放入间歇低氧箱内，模型组和加味涤痰汤组通过电脑程序设定调控氧浓度造模，每天8 h，正常组通入相同流量的空气。连续干预12周建立慢性间歇低氧大鼠模型。采用Y迷宫测试评估大鼠空间工作记忆能力；静息态功能磁共振成像（rs-fMRI）检测大鼠全脑局部一致性（ReHo）及基于种子点的功能连接（FC）；选取rs-fMRI中具有统计学差异的脑区，采用免疫荧光法检测β淀粉样蛋白（Aβ）沉积与小胶质细胞标记物离子钙结合适配器分子1（IBA1）阳性细胞数量，免疫组化法检测突触体素（SYP）、兴奋性突触标记物囊泡谷氨酸转运体1（Vglut1）和抑制性突触标记物囊泡γ氨基丁酸转运体（VGAT）的表达。

结果

与正常组比较，模型组Y迷宫自发交替率降低，左侧内嗅皮层平滑后的

值标准化的局部一致性（SzReHo）值显著升高，以此为种子点至左侧基底前脑的FC值显著降低，左侧内嗅皮层Aβ荧光强度及Iba1阳性率显著升高，SYP、Vglut1、VGAT表达降低，Vglut1/VGAT比值升高（

＜0.05或

＜0.01）。与模型组比较，加味涤痰汤组自发交替率升高，左侧内嗅皮层SzReHo值显著降低，以此为种子点至左侧基底前脑的FC值显著升高，左侧内嗅皮层Aβ荧光强度和Iba1阳性率显著降低，SYP、Vglut1、VGAT水平升高，Vglut1/VGAT比值降低（

＜0.05或

＜0.01）。

结论

加味涤痰汤可重建慢性间歇低氧状态下左侧基底前脑至内嗅皮层的投射，进而减轻左侧内嗅皮层Aβ聚集和小胶质细胞的过度活化，改善突触重塑引起的兴奋/抑制失衡，从而改善慢性间歇低氧大鼠认知功能。

Abstract

Objective

To explore the effect of modified

Ditan Decoction

（涤痰汤） on chronic intermittent hypoxia cognitive function and the potential function mechanism.

Methods

Twenty-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 thre

e 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）.

Results

Compared 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 （

＜0.05 or

＜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 t

his 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 （

＜0.05 or

＜0.01）.

Conclusion

Modified

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.

关键词

Keywords

references

PATEL SR . Obstructive sleep apnea ［J］. Ann Intern Med ， 2019 ， 171 （ 11 ）： ITC81 - ITC96 .

赵洋，杨胜昌，吉恩生 . 阻塞性睡眠呼吸暂停的中医药治疗研究进展［J］. 中国中医基础医学杂志， 2021 ， 27 （ 3 ）： 531 - 534 .

陈沁，林劲榕，洪旭初，等 . 加味涤痰汤对老年阻塞性睡眠呼吸暂停低通气综合征患者氧化应激和炎性反应的干预作用［J］. 中华老年医学杂志， 2015 ， 34 （ 7 ）： 715 - 719 .

陈乃洁，王小婷，徐峰圣，等 . 加味涤痰汤对慢性间歇性缺氧大鼠认知功能影响及作用机制研究［J］. 福建中医药， 2023 ， 54 （ 2 ）： 20 - 25 .

WEI Z ， YUE J ， LI X ， et al . A mini-review on functional magnetic resonance imaging on brain structure of vascular cognitive impairment ［J］. Front Neurol ， 2023 ， 14 ： 1249147 . doi： 10.3389/fneur.2023.1249147 http://dx.doi.org/10.3389/fneur.2023.1249147 .

汤家铭，陈民利 . 医学实验动物学［M］. 北京：中国中医药出版社， 2012 ： 209 - 210 .

CHEN J ， ZHU H ， CHEN Q ， et al . The role of ferroptosis in chronic intermittent hypoxia-induced lung injury ［J］. BMC Pulm Med ， 2022 ， 22 （ 1 ）： 488 .

HUGHES RN . The value of spontaneous alternation behavior （SAB） as a test of retention in pharmacological investigations of memory ［J］. Neurosci Biobehav Rev ， 2004 ， 28 （ 5 ）： 497 - 505 .

DONG J ， YU X ， WANG Y ， et al . Obstructive sleep apnea and cognition： insights gleaned from bibliometric ana-lysis ［J］. Front Psychiatry ， 2023 ， 14 ： 1259251 . doi： 10. 3389/fpsyt.2023.1259251 http://dx.doi.org/10.3389/fpsyt.2023.1259251 .

MARCHI NA ， SOLELHAC G ， BERGER M ， et al . Obstructive sleep apnoea and 5-year cognitive decline in the elderly ［J］. Eur Respir J ， 2023 ， 61 （ 4 ）： 2201621 .

宁云红，王仁忠，孟伟 . 基于"阳化气，阴成形"理论探讨儿童鼾症的证治［J］. 中医药导报， 2023 ， 29 （ 1 ）： 177 - 179，184 .

李然，张海滨，王振裕 . 阻塞性睡眠呼吸暂停患者中医证型分布规律及特征分析［J］. 北京中医药， 2022 ， 41 （ 11 ）： 1287 - 1290 .

RAIMONDO L ， ĹAFOLIVEIRA ， HEIJ J ， et al . Advances in resting state fMRI acquisitions for functional connectomics ［J］. Neuroimage ， 2021 ， 243 ： 118503 . doi： 10. 1016/j.neuroimage.2021.118503 http://dx.doi.org/10.1016/j.neuroimage.2021.118503 .

NI S ， GAO S ， LING C ， et al . Altered brain regional homogeneity is associated with cognitive dysfunction in first-episode drug-naive major depressive disorder： a resting-state fMRI study ［J］. J Affect Disord ， 2023 ， 343 ： 102 - 108 . doi： 10.1016/j.jad.2023.10.003 http://dx.doi.org/10.1016/j.jad.2023.10.003 .

CHEN G ， CHEN P ， YANG Z ， et al . Increased functional connectivity between the midbrain and frontal cortex following bright light therapy in subthreshold depression： A randomized clinical trial ［J］. Am Psychol ， 2023 ， 79 （ 3 ）： 437 - 450 .

DESIKAN S ， KOSER DE ， NEITZ A ， et al . Target selectivity of septal cholinergic neurons in the medial and lateral entorhinal cortex ［J］. Proc National Acad Sci U S A ， 2018 ， 115 （ 11 ）： E2644 - E2652 .

MIELING M ， GÖTTLICH M ， YOUSUF M ， et al . Basal forebrain activity predicts functional degeneration in the entorhinal cortex in Alzheimer's disease ［J］. Brain Comm ， 2023 ， 5 （ 5 ）： fcad262 .

IGARASHI KM . Entorhinal cortex dysfunction in Alzheimer's disease ［J］. Trends Neurosci ， 2023 ， 46 （ 2 ）： 124 - 136 .

GERMAN-CASTELAN L ， SHANKS HRC ， GROS R ， et al . Sex-dependent cholinergic effects on amyloid pathology： a translational study ［J］. Alzheimers Dement ， 2024 ， 20 （ 2 ）： 995 - 1012 .

NIZARI S ， WELLS JA ， CARARE RO ， et al . Loss of cholinergic innervation differentially affects eNOS-mediated blood flow， drainage of Aβ and cerebral amyloid angio-pathy in the cortex and hippocampus of adult mice ［J］. Acta neuropathol Commun ， 2021 ， 9 （ 1 ）： 12 .

CAMPOS-PEñA V ， PICHARDO-ROJAS P ， SÁNCHEZ-BARBOSA T ， et al . Amyloid β， lipid metabolism， basal cholinergic system， and therapeutics in Alzheimer's disease ［J］. Int J Mol Sci ， 2022 ， 23 （ 20 ）： 12092 .

SOOD A ， PREETI K ， FERNANDES V ， et al . Glia： a major player in glutamate-GABA dysregulation-mediated neurodegeneration ［J］. J Neurosci Res ， 2021 ， 99 （ 12 ）： 3148 - 3189 .

MIYANISHI K ， SATO A ， KIHARA N ， et al . Synaptic elimination by microglia and disturbed higher brain functions ［J］. Neurochem Int ， 2021 ， 142 ： 104901 . doi： 10. 1016/j.neuint.2020.104901 http://dx.doi.org/10.1016/j.neuint.2020.104901 .

GHATAK S ， TALANTOVA M ， MCKERCHER SR ， et al . Novel therapeutic approach for excitatory/inhibitory imbalance in neurodevelopmental and neurodegenerative diseases ［J］. Ann Rev Pharmacol Toxicol ， 2021 ， 61 ： 701 - 721 . doi： 10.1146/annurev-pharmtox-032320-015420 http://dx.doi.org/10.1146/annurev-pharmtox-032320-015420 .

KAZIM SF ， SEO JH ， BIANCHI R ， et al . Neuronal network excitability in Alzheimer's disease： the puzzle of similar versus divergent roles of amyloid β and tau ［J］. eNeuro ， 2021 ， 8 （ 2 ）：ENEURO. 0418 - 20 .2020. doi： 10.1523/ENEURO.0418-20.2020 http://dx.doi.org/10.1523/ENEURO.0418-20.2020 .

SCADUTO P ， LAUTERBORN JC ， COX CD ， et al . Functional excitatory to inhibitory synaptic imbalance and loss of cognitive performance in people with Alzheimer's disease neuropathologic change ［J］. Acta Neuropathol ， 2023 ， 145 （ 3 ）： 303 - 324 .

BI D ， WEN L ， WU Z ， et al . GABAergic dysfunction in excitatory and inhibitory （E/I） imbalance drives the pathogenesis of Alzheimer's disease ［J］. Alzheimers Dement ， 2020 ， 16 （ 9 ）： 1312 - 1329 .

CAPSONI S ， ARISI I ， MALERBA F ， et al . Targeting the cation-chloride co-transporter nkcc1 to re-establish GABAergic inhibition and an appropriate excitatory/inhibitory balance in selective neuronal circuits： a novel approach for the treatment of Alzheimer's disease ［J］. Brain Sci ， 2022 ， 12 （ 6 ）： 783 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effects of Tongluo Fuzheng Decoction （通络扶正汤） as an Adjunctive Therapy on Coagulation and Vascular Endothelial Function in Patients with Ischemic Stroke of the Acute Stage with Wind-Phlegm and Blood Stasis Syndrome

Effect of Tuina at "Weizhong （BL 40）" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury

Effect of Tongnao Yizhi Formula （通脑益智方） on Cognitive Function and Gut Microflora in Treating Vascular Cognitive Impairment No Dementia Patients with Spleen and Kidney Depletion，Phlegm and Stasis Obstructing Collaterals Syndrome

Effects of Erxian Decoction （二仙汤） on Choroid Plexus Folate Transport-Hippocampal Neurogenesis in Rat Brain Tissue of Late-Onset Depression Model

Effects of Acupuncture on Functional Connectivity Changes of What Visual Pathway in the Brain in Children with Monocular Refractive Amblyopia

Related Author

LI Zhengliang

LIU Lijun

ZHANG Yongqiang

ZHANG Tianwei

LYU Xiangqian

XING Yani

ZHU Liuchen

ZHU Qingguang

Related Institution

Huaihe Hospital，Henan University

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Institute of Tuina，Shanghai Academy of Traditional Chinese Medicine

School of Traditional Chinese Medicine，Shanghai University of Traditional Chinese Medicine

School of Acupucture-Moxibustion and Tuina，Shanghai University of Traditional Chinese Medicine

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

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

DOI：10.13288/j.11-2166/r.2025.01.012

摘要

Abstract

关键词

Keywords

references