中国中药杂志2026,Vol.51Issue(4):1064-1071,8.DOI:10.19540/j.cnki.cjcmm.20250723.401
无忧汤通过抑制神经炎症及保护血脑屏障改善慢性睡眠剥夺模型大鼠海马损伤的机制研究
Mechanism of Wuyou Decoction in improving hippocampal injury in chronic sleep deprivation model rats by inhibiting neuroinflammation and protecting blood-brain barrier
摘要
Abstract
This study explored the mechanism by which Wuyou Decoction(WYD)ameliorated hippocampal injury in a chronic sleep deprivation model rat by suppressing neuroinflammation and protecting the blood-brain barrier(BBB).Fifty 2-month-old male SD rats were randomly divided into five groups:normal,model,low-dose WYD,medium-dose WYD,and high-dose WYD.Except for the normal group,all rats underwent a 7-day adaptation period for the water platform sleep deprivation model,which was followed by 21 days of formal sleep deprivation modeling.Concurrently with the start of formal modeling,rats in the low-,medium-,and high-dose WYD groups received corresponding doses of WYD via intragastric administration for 28 consecutive days.After modeling and drug administration,learning and memory were assessed using the Morris water maze.Nissl staining was used to quantify Nissl bodies.Immunohistochemistry evaluated the morphology and quantity of the neuronal marker neuron specific nuclear protein(NeuN)in the hippocampus.Enzyme-linked immunosorbent assay(ELISA)measured levels of amyloid β-protein(Aβ)1-40 and Aβ1-42.Immunofluorescence assessed the fluorescence intensity of ionized calcium-binding adapter molecule 1(IBA1)and glial fibrillary acidic protein(GFAP).Western blot analyzed the expression of matrix metalloproteinase 2(MMP2),matrix metalloproteinase 9(MMP9),zona occludens 1(ZO-1),claudin 5,occludin,interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α in hippocampal tissue,which were proteins related to BBB and inflammatory factors.Compared with the normal group,the model group exhibited significantly prolonged escape latency and decreased platform-crossing times and target quadrant residence time.Nissl body count and NeuN-positive neurons were reduced with disorganized neuronal arrangement.Aβ1-40 and Aβ1-42 levels were elevated.Fluorescence intensity of IBA1 and GFAP was increased.Expression of inflammatory factors IL-1β,IL-6,and TNF-α was enhanced,and expression of MMP9 and MMP2 was upregulated,while expression of ZO-1,occludin,and claudin 5 was downregulated.Compared to the model group,medium-dose WYD intervention shortened escape latency and increased platform-crossing times and target quadrant residence time.Nissl bodies and neurons were more numerous and were orderly arranged.Aβ1-40 and Aβ1-42 levels were reduced.Fluorescence intensity of IBA1 and GFAP was attenuated.Levels of IL-1β,IL-6,and TNF-α were decreased.Expression of MMP9 and MMP2 was downregulated,while expression of ZO-1,occludin,and claudin 5 was upregulated.The above results suggest that WYD improves cognitive function in the chronic sleep deprivation model rats by inhibiting the release of pro-inflammatory cytokines and protecting the integrity of BBB.关键词
无忧汤/慢性睡眠剥夺/血脑屏障/神经炎症/机制研究Key words
Wuyou Decoction/chronic sleep deprivation/blood-brain barrier/neuroinflammation/mechanism study引用本文复制引用
王政喻,高建红,吴丹,赖碧璇,蔡元钦,王曦,龙清华..无忧汤通过抑制神经炎症及保护血脑屏障改善慢性睡眠剥夺模型大鼠海马损伤的机制研究[J].中国中药杂志,2026,51(4):1064-1071,8.基金项目
国家自然科学基金项目(82204964) (82204964)
中国博士后科学基金面上项目(2025M773957) (2025M773957)
湖北民族大学研究生创新项目(MYK2023060) (MYK2023060)