健脑固本方对脑小血管性认知障碍大鼠神经血管单元的保护作用及机制  

Protective effects and mechanism of Jiannao Guben Formula on neurovascular unit in cerebral small vessel cognitive impairment rats

作　　者：胡玉立 韩振蕴[2,3] 王育纯 曾伟坤 田丹枫 常泽 胡文悦 马华萍 HU Yuli;HAN Zhenyun;WANG Yuchun;ZENG Weikun;TIAN Danfeng;CHANG Ze;HU Wenyue;MA Huaping(Shenzhen Hospital,Beijing University of Chinese Medicine(Longgang),Shenzhen 518172,China;Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学深圳医院(龙岗),深圳518172 [2]北京中医药大学,北京100029 [3]北京中医药大学东方医院,北京100078

出　　处：《中华中医药杂志》2024年第11期6032-6036,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82274466);广东省自然科学基金项目(No.2023A1515011140);深圳市“医疗卫生三名工程”(No.SZZYSM202105010);中国博士后科学基金(No.262677);新教师课题(No.2023-JYB-XJSJJ047)。

摘　　要：目的:探究健脑固本方对脑小血管性认知障碍(CSVCI)大鼠神经血管单元(NVU)的保护作用及机制。方法:采用双侧颈总动脉闭塞法制备CSVCI大鼠模型,随机分为假手术组、模型组、多奈哌齐组、健脑固本方组,每组8只。假手术组和模型组大鼠予0.9%氯化钠溶液灌胃,多奈哌齐组和健脑固本方组大鼠分别予多奈哌齐混悬液0.45 mg·kg^(-1)·d^(-1)和健脑固本方药液7.1 g·kg^(-1)·d^(-1)灌胃,给药4周。水迷宫测试大鼠学习记忆能力。HE、尼氏及固蓝染色观察皮质神经元及胼胝体白质病理变化。免疫组化观察脑组织Claudin5、Occludin、vWF、ICAM-1蛋白变化,免疫荧光观察MBP、GFAP、IBA1蛋白变化。结果:与模型组比较,健脑固本方组大鼠水迷宫平均逃避潜伏期显著减少(P<0.05),平台区域路程比和穿越平台次数显著增加(P<0.05,P<0.01);神经元病变改善,尼氏体增多,胼胝体髓鞘致密规则;大鼠脑组织MBP、Claudin5、Occludin显著升高(P<0.01,P<0.05),vWF、ICAM-1、GFAP和IBA1表达显著下调(P<0.05,P<0.01),激活的星型胶质细胞和小胶质细胞突起减少,胞体变小,距离增加,相互作用减少。结论:CSVCI大鼠存在NVU损伤,契合“毒损脑络”理论,健脑固本方可通过修复NVU损伤从而达到改善认知功能的作用。Objective:To explore the protective effect and mechanism of Jiannao Guben Formula(JNGB)on the neurovascular unit(NVU)in rats with cerebral small vessel cognitive impairment(CSVCI).Methods:The CSVCI rat model was prepared using bilateral common carotid artery occulsion method.The rats were randomly divided into sham group,model group,donepezil group and JNGB group,with 8 rats in each group.Rats in the sham group and model group were given normal saline by gavage,while rats in the donepezil group and JNGB group were given donepezil suspension and JNGB by gavage respectively.After 4 weeks of administration,the Morris water maze was performed to examine the learning and memory abilities of the rats.HE,Nissl and LFB staining were performed to observe the pathological changes of cortical neurons and myelin sheath.Immunohistochemical and immunofluorescence were used to detect proteins expression of Claudin5,Occludin,vWF,ICAM-1,MBP,GFAP and IBA1 in rats.Results:Compared with the model group,the average escape latency of the water maze of the rats in the JNGB group decreased(P<0.05)and the distance ratio of platform area and the number of times crossed the platform increased(P<0.05,P<0.01).The pathological changes of neurons were ameliorated,the number of Nissl bodies was increased,and the myelin sheaths of corpus callosum were denser and regular.Furthermore,JNGB supplement could increase the protein expressions of MBP,Claudin-5,Occludin(P<0.05,P<0.01)and decrease the expression of vWF,ICAM-1,GFAP and IBA1(P<0.01,P<0.05).Besides,the distance between activated astrocytes and microglia was increased,and the interaction was reduced.Conclusion:There are NVU damages in CSVCI rats,which is accordance with the theory of‘toxic damage to the brain meridians’,and JNGB can improve cognitive function by repairing NVU damage.

关 键 词：毒损脑络 健脑固本方 脑小血管性认知障碍 神经血管单元 血脑屏障 胶质细胞活化 血管内皮损伤 

分 类 号：R285.5[医药卫生—中药学]