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颐脑通络方调控小胶质细胞活化介导炎症反应治疗血管性痴呆机制研究
陈雨菲1, 李小黎1, 李倩倩2, 刁华琼1, 李晓路1, 曲淼1
1.北京中医药大学第三附属医院, 北京 100029;2.首都医科大学附属北京中医医院, 北京 100010
摘要:
[目的] 探究颐脑通络方对血管性痴呆(VaD)大鼠学习记忆能力的影响及作用机制。[方法] 通过双侧颈总动脉结扎手术建立VaD大鼠模型,分别设置假手术组、模型组、西药组、颐脑通络方低、中、高剂量组,均干预28 d。通过Morris水迷宫实验检测大鼠学习记忆能力,苏木精-伊红(HE)染色观察海马组织形态,酶联免疫吸附(ELISA)法检测海马组织白细胞介素(IL)-1β、IL-10含量,结合免疫荧光观察小胶质细胞激活情况。[结果] 与假手术组比较,模型组大鼠逃避潜伏期增加,平台所在象限路程百分比及时间百分比减少(P<0.05),海马组织神经元数量减少,锥体细胞丢失,细胞层结构疏松,排列紊乱,细胞核固缩,IL-1β含量增加(P<0.05),IL-10含量减少(P<0.05),CD68+小胶质细胞含量增加(P<0.05)。与模型组比较,颐脑通络方低、中、高剂量组大鼠逃避潜伏期减少(P>0.05),颐脑通络方高剂量组平台所在象限路程百分比及时间百分比减少(P<0.05),颐脑通络方低、中、高剂量组海马组织神经元损伤程度减轻,神经元数量增多,排列整齐,细胞较为完整,颐脑通络方低、中、高剂量组IL-1β含量减少(P<0.05),IL-10含量增加(P<0.05),颐脑通络方高剂量组CD68+小胶质细胞含量减少(P<0.05)。[结论] 颐脑通络方可能通过抑制小胶质细胞激活,减轻神经炎症,改善VaD认知功能障碍。
关键词:  颐脑通络方  血管性痴呆  小胶质细胞  神经炎症  细胞因子
DOI:10.11656/j.issn.1673-9043.2025.07.07
分类号:R743.9
基金项目:国家自然科学基金青年项目(82104997);北京中医药大学第三附属医院“精诚人才计划”项目;北京中医药新时代125工程项目。
Mechanism of Yinao Tongluo Formula in treating vascular dementia by regulating microglia-mediated neuroinflammation
CHEN Yufei1, LI Xiaoli1, LI Qianqian2, DIAO Huaqiong1, LI Xiaolu1, QU Miao1
1.The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100029, China;2.Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
Abstract:
[Objective] To investigate the therapeutic mechanism of Yinao Tongluo Formula(YTF) on vascular dementia(VaD) through microglial activation-mediated neuroinflammation regulation. [Methods] VaD model was induced by bilateral common carotid artery occlusion(BCCAO). Rats were divided into:sham-operated,model,western medicine(donepezil 1 mg/kg),and YTF low-(3 g/kg),medium-(6 g/kg),and high-dose(12 g/kg) groups(n=12/group) for 28-days treatment. Cognitive function was assessed by Morris water maze test. Hippocampal morphology was examined via hematoxylin-eosin(HE) staining. Interleukin(IL)-1β and IL-10 levels were measured by ELISA. Microglial activation was evaluated using CD68 immunofluorescence. [Results] Compared with sham group,model group showed:prolonged escape latency(P<0.05),reduced platform quadrant residence time/distance(P<0.05),hippocampal neuronal loss with pyramidal cell degeneration,increased IL-1β(P<0.05) and decreased IL-10(P<0.05). Elevated CD68+ microglia(P<0.05). YTF treatment significantly:improved cognitive performance(high-dose most effective,P<0.05),preserved neuronal architecture with dose-dependent effects,reduced IL-1β and increased IL-10(all doses,P<0.05),suppressed microglial activation(high-dose,P<0.05). [Conclusion] YTF ameliorates VaD by inhibiting microglia-mediated neuroinflammation,possibly through IL-1β/IL-10 pathway modulation.
Key words:  Yinao Tongluo Formula  vascular dementia  microglia  neuroinflammation  cytokine
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