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  

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

作　　者：陈乃洁[1] 王小婷[2] 徐峰圣 沈双宏 李钻芳[4] 陈沁[2] 陈进 吴润华 CHEN Naijie;WANG Xiaoting;XU Fengsheng;SHEN Shuanghong;LI Zuanfang;CHEN Qin;CHEN Jin;WU Runhua(College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122;Clinical Skill Center,Fujian University of Traditional Chinese Medicine;Affiliated People′s Hospital,Fujian University of Traditional Chinese Medicine;Science and Technology Innovation and Transformation Center,Fujian University of Traditional Chinese Medicine)

机构地区：[1]福建中医药大学中西医结合学院,福建福州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

出　　处：《中医杂志》2025年第1期71-78,共8页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82305139);福建省自然科学基金(2023J01826)。

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Z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(P<0.05或P<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(P<0.05或P<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。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 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 detectβ-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 vesicularγ-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 si

关 键 词：慢性间歇低氧 阻塞性睡眠呼吸暂停低通气综合征 认知功能 静息态功能磁共振成像 内嗅皮层 Β淀粉样蛋白 小胶质细胞 加味涤痰汤 

分 类 号：R285.5[医药卫生—中药学]