西部中医药2025，Vol.38Issue(6)：22-28,7.DOI:10.12174/j.issn.2096-9600.2025.06.05
通窍益智颗粒通过Ca2+/CaMK Ⅱ信号通路改善血管性痴呆大鼠海马CA1区突触可塑性机制研究
Study on the Mechanism of Synaptic Plasticity in the Hippocampal CAⅠ Region of Vascular Dementia Rats by Tongqiao Yizhi Granules via Ca2+/CaMK Ⅱ Signaling Pathway
摘要
Abstract
Objective:To explore the relevant mechanism of Tongqiao Yizhi(orifice-unobstructing wisdom-benefiting)granules in the treatment of vascular dementia(VaD).Methods:A total of 92 SD rats were selected,among them,12 rats were included as sham operation group,and the remaining 80 rats were prepared into VaD models using bilateral permanent ligation of the common carotid artery,62 rats,after successfully modeling,were screened,and divided into the model group,memantine group,high and moderate doses groups of Tongqiao Yizhi granules according to random number table method with ten rats in each group.Sham operation group and the model group were drenched with physiological saline;memantine group accepted intragastric administration of memantine,1.04 mg/(kg·d);high and moderate doses groups of Tongqiao Yizhi granules were given the granules,9.68 and 4.84 g/(kg·d),for gastric lavage respectively,twice each day,for 30 days continuously.Morris water maze was adopted to assess behavioral changes in rats;transmission electron microscopy was used to observe synaptic structure of the neuron in the hippocampal CAI region of the rats;flow cytometry was applied to detect fluorescence intensity of Ca2+in hippocampal neurons of the rats;immunofluorescence was utilized to measure the expressions of NMDA receptor subunit Glu N1,Glu N2B and AMPA receptor subunit Glu A2 in hippocampal CAI region;Western blot was used to check the expressions of Glu N1,Glu N2B,Glu A2 and CaMKⅡ,and p CaMKⅡprotein.Results:Compared with sham operation group,the time spent swimming shortened in the target quadrant and the number of platform crossings decreased,while the concentrations of Ca2+in the neurons increased in the model group,the expressions of Glu N1,Glu N2B and Glu A2,and p CaMKⅡ protein lowered in hippocampal CAI region(P＜0.05).EL time prolonged in the model group on the fifth day of the experiment(P＜0.05);compared with the model group,the swimming time spent in the target quadrant prolonged and the number of platform crossings increased,the density of Ca2+in the neurons decreased,the expressions of Glu N1,Glu N2B and Glu A2,and p CaMKⅡ raised in hippocampal CAI region in memantine group,high and moderate dose groups of Tongqiao Yizhi granules(P＜0.05).EL time shortened in memantine group,high and moderate dose groups of Tongqiao Yizhi granules on the fifth day of the experiment(P＜0.05).The improvements of the indexes were more significant in high dose group of Tongqiao Yizhi granules when compared with memantine group and moderate dose group of Tongqiao Yizhi granules(P＜0.05).The synaptic cleft in CA1 region of rat hippocampus was blurred,the presynaptic and postsynaptic membranes were swollen,the structure was difficult to distinguish,the synaptic active area was reduced,and mitochondrial structure within the cells was destroyed in the rats of the model group;Synaptic structure was improved in memantine group,high and moderate dose groups of Tongqiao Yizhi granules,synaptic membrane structure was relatively complete,synaptic cleft was more clear,synaptic vesicles were increased in memantine group,high and moderate dose groups of Tongqiao Yizhi granules,complete mitochondria could be seen within the cells,and the improvements of high dose group of the granules were the best.Conclusion:Tongqiao Yizhi granules based on"sweating pore theory"could improve learning and memory ability in VaD rat models,and synaptic structure of the neurons in hippocampal CAⅠ region,and its potential mechanism might be related to that it could regulate Ca2+/CaMKⅡ signaling pathways and improve synaptic plasticity.关键词
血管性痴呆/玄府/钙离子/磷酸化钙调蛋白依赖性蛋白激酶/突触可塑性/通窍益智颗粒Key words
vascular dementia/sweating pore/Ca2+/phosphorylated calcium modulated protein-dependent protein kinase/synaptic plasticity/Tongqiao Yizhi granules分类
医药卫生引用本文复制引用
陆叶,袁媛,李双阳,王饶琼,唐红梅,白雪..通窍益智颗粒通过Ca2+/CaMK Ⅱ信号通路改善血管性痴呆大鼠海马CA1区突触可塑性机制研究[J].西部中医药,2025,38(6):22-28,7.基金项目
四川省中医药管理局科研专项(川中医药函[2020]196号) （川中医药函[2020]196号）
西南医科大学附属中医医院联合项目(2018XYLH-006) （2018XYLH-006）
西南医科大学附属中医医院科研项目(西南医大中医院[2019]119号) （西南医大中医院[2019]119号）
泸州市科技计划项目(2022-SYF-34). （2022-SYF-34）
