加减薯蓣丸上调MyRF减轻血管性痴呆小鼠mPFC-BLA环路髓鞘损伤及焦虑抑郁行为  

Modified Shuyu Pills Alleviates Myelin Damage in the mPFC-BLA Circuit and Mitigate Anxiety and Depression Behaviors in Vascular Dementia Mice through MyRF Upregulation

作　　者：陈欣怡 冯小霞 陈晨 邱静 谭子虎 阳光 CHEN Xin-yi;FENG Xiao-xia;CHEN Chen;QIU Jing;TAN Zi-hu;YANG Guang(The First Clinical Medical School of Hubei University of Chinese Medicine,Wuhan,430061;Department of Geriatrics,Hubei Provincial Hospital of Traditional Chinese Medicine,Affiliated Hospital of Hubei University of Chinese Medicine,Hubei Provincial Institute of Traditional Chinese Medicine,Wuhan,430061)

机构地区：[1]湖北中医药大学第一临床学院,武汉430061 [2]湖北省中医院老年病科/湖北中医药大学附属医院/湖北省中医药研究院,武汉430061

出　　处：《中国中西医结合杂志》2025年第1期90-99,共10页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：湖北省自然科学基金面上项目(No.2021CFB533);国家自然科学基金面上项目(No.82274334);武汉市应用基础前沿项目(No.2020020601012244)。

摘　　要：目的探讨加减薯蓣丸(MSP)改善血管性痴呆(VaD)小鼠焦虑、抑郁行为的机制。方法在药效研究中,选择60只C57BL/6小鼠,以颈总动脉缩窄/束缚应激(BCAS/CRS)构建VaD行为异常模型,假手术处理作为对照。按干预条件分为对照组(生理盐水)、模型组(生理盐水)、MSP组(7、14、28 g/kg)、氟西汀(10 mg/kg)组。在机制研究中,40只BCAS/CRS模型小鼠,分别接受空载病毒、髓鞘基因调节因子(MyRF)过表达病毒、MSP(14 g/kg)、MSP+MyRF敲低病毒处理。旷场实验、高架十字迷宫实验、悬尾实验评估行为学变化;Western Blot检测髓鞘相关糖蛋白(MAG)、髓鞘少突胶质细胞糖蛋白(MOG)、髓鞘碱性蛋白(MBP)及髓鞘基因调节因子(MyRF)表达;免疫荧光染色检测MBP表达;胼胝体复合动作电位记录评估有髓轴突动作电位传导。结果与对照组比较,模型组小鼠开放臂次数/时间、中央区时间/距离减少,不动时间延长(P<0.01);mPFC和BLA脑区MAG、MOG、MBP和MyRF表达降低(P<0.01),MBP荧光强度和动作电位N1振幅降低(P<0.01)。MSP及氟西汀增加模型小鼠开放臂次数/时间和中央区时间/距离,缩短不动时间(P<0.01,P<0.05),上调髓鞘相关蛋白及MyRF表达(P<0.01,P<0.05),增加MBP荧光强度和动作电位N1振幅(P<0.01)。MyRF敲低减弱了MSP对模型小鼠行为学、髓鞘相关蛋白表达和动作电位N1振幅的改善效应(P<0.01,P<0.05)。结论加减薯蓣丸通过上调mPFC-BLA环路MyRF表达,促进髓鞘修复和信号传导,改善VaD小鼠焦虑和抑郁行为。Objective To investigate the mechanism of modified Shuyu Pills(MSP)in alleviating anxiety and depression behaviors in vascular dementia(VaD)mice.Methods For the pharmacological study,60 C57BL/6 mice were utilized to establish the VaD model through common carotid artery constriction/restraint stress(BCAS/CRS),with a sham operation serving as the control.Based on intervention conditions,the mice were divided into the control group(normal saline),model group(normal saline),MSP group(7,14,28 g·kg-1),and fluoxetine group(10 mg·kg-1).For the mechanism study,40 BCAS/CRS mice were treated with empty virus,MyRF overexpression virus,MSP(14 g·kg-1),and MSP+MyRF knockdown virus,respectively.Behavioral changes were evaluated using the open-field test,elevated plus maze test,and tail suspension test.Western Blot analysis was employed to detect the expression of Myelinassociated glycoprotein(MAG),Myelin oligodendrocyteglycoprotein(MOG),Myelinbasic protein(MBP)and Myelin-generegulatory factors(MyRF).MBP expression was also assessed through immunofluorescence staining.Compound action potential recordings in the corpus callosum were conducted to evaluate the conductive efficacy of action potential in myelinated axons.Results Compared with the control group,the number/time of opening arms and the time/distance of the central area in the model group were significantly decreased,and the immobility time was prolonged(P<0.01).Expressions of MAG,MOG,MBP,and MyRF in mPFC and BLA were reduced,along with decreased MBP fluorescence intensity and action potential N1 amplitude(P<0.01).MSP and fluoxetine significantly increased the number/time of opening arms and the time/distance of the central area,while shortening the immobility time(P<0.01,P<0.05).MSP and fluoxetine induced upregulation of myelin associated protein and MyRF expression,as well as changes in MBP fluorescence intensity and action potential N1 amplitude(P<0.01,P<0.05).MyRF knockdown attenuated the improvement effect of MSP on the behavior,myelin-related protein expression,a

关 键 词：加减薯蓣丸 髓鞘 血管性痴呆 情绪环路 焦虑抑郁 行为异常 中药复方 氟西汀 

分 类 号：R285.5[医药卫生—中药学]