| 本文已被：浏览 410次 下载 226次 |
码上扫一扫！ |
|
|
| 八桂天龙散调节小胶质细胞M1/M2极化改善血管性认知障碍的作用机制 |
|
陈洁1,2, 陈宇1, 刘轶群1, 韦熔煌1, 郝二伟1, 付蕾1,2,3, 姚春1,2,3
|
|
1.广西中医药大学, 南宁 530200;2.广西中医基础研究重点实验室, 南宁 530200;3.区域重大病种创新产品研发广西高校工程研究中心, 南宁 530200
|
|
| 摘要: |
| [目的] 基于小胶质细胞 M1/M2 极化探讨八桂天龙散改善血管性认知障碍（VCI）的作用机制。[方法] 通过双侧颈总动脉结扎法建立 VCI 大鼠模型，随机分为模型组、八桂天龙散组、多奈哌齐组和假手术组。药物干预4 周后，采用旷场实验评价大鼠自发活动，Morris 水迷宫检测学习记忆功能；激光微循环成像检测脑血流灌注；HE 及尼氏染色观察海马病理形态；血清生化检测肝肾功能；ELISA 检测血清及海马组织白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平；实时荧光定量 PCR（qRT-PCR）检测海马组织小胶质细胞极化标志物离子钙结合衔接分子 1（IBA1）、诱导型一氧化氮合酶（iNOS）、精氨酸酶 1（ARG1）及炎症因子 mRNA 表达；免疫荧光检测海马 IBA1、iNOS、ARG1 蛋白表达。[结果] 与模型组相比，八桂天龙散组大鼠总路程、平均速度、中央时间和中央路程增加（P<0.05）；水迷宫逃避潜伏期显著缩短（P<0.01），穿越平台次数、目标象限的停留时间、目标象限时间比及目标象限路程比均显著增加（P<0.05）；脑血流灌注改善（P<0.01）；海马损伤及尼氏体丢失减轻；无肝肾损伤。八桂天龙散组 IL-1β、IL-6、TNF-α 水平降低（P<0.01）；IBA1、iNOS 及炎症因子 mRNA 表达下调，ARG1 mRNA 表达上调，炎症因子 mRNA 表达下调（P<0.05）；免疫荧光显示 IBA1+、iNOS+表达减少，ARG1+表达增多（P<0.05），iNOS+/ARG1+比值降低（P<0.01）。[结论] 八桂天龙散可能通过调控小胶质细胞 M1/M2 极化稳态、抑制神经炎症反应，从而改善 VCI 大鼠的认知功能。 |
| 关键词: 八桂天龙散 血管性认知障碍 小胶质细胞 细胞极化 神经炎症 |
| DOI：10.11656/j.issn.1672-1519.2026.10.10 |
| 分类号:R285.5 |
| 基金项目:国家重点研发计划（2024YFC3506700）；广西科技创新平台计划（桂科LT2600640035）；国家岐黄学者培养项目（国中医药人教函〔2025〕182号）；广西岐黄学者培养支持项目（GXQH202404）；姚春桂派中医大师传承工作室（GZY2024002）；广西道地药材资源开发与利用人才小高地（第十批广西人才小高地）。 |
|
| Mechanism of Bagui Tianlong Powder in ameliorating vascular cognitive impairment by regulating microglial M1/M2 polarization |
|
CHEN Jie1,2, CHEN Yu1, LIU Yiqun1, WEI Ronghuang1, HAO Erwei1, FU Lei1,2,3, YAO Chun1,2,3
|
|
1.Guangxi University of Chinese Medicine, Nanning 530200, China;2.Guangxi Key Laboratory of Chinese Medicine Foundation Research, Nanning 530200, China;3.Guangxi Universities Engineering Research Center for Innovative Product Development of Regional Priority Diseases, Nanning 530200, China
|
| Abstract: |
| [Objective] To investigate the mechanism of Bagui Tianlong Powder（BGTLP）in improving vascular cognitive impairment （VCI）based on microglial M1/M2 polarization. [Methods] A VCI rat model was established by bilateral common carotid artery occlusion（2VO）. Rats were randomly divided into model group，Bagui Tianlong group，donepezil group，and sham operation group. After 4 weeks of drug intervention，spontaneous locomotor activity was evaluated by open field test，and learning and memory function was assessed by Morris water maze. Cerebral blood flow perfusion was detected by laser speckle contrast imaging. Hippocampal pathological morphology was observed by hematoxylin-eosin（HE）and Nissl staining. Serum biochemical parameters were measured to evaluate liver and kidney functions. Levels of interleukin-1β（IL-1β），interleukin-6（IL-6），and tumor necrosis factor-α（TNF-α）in serum and brain tissue were detected by enzyme-linked immunosorbent assay（ELISA）. The mRNA expression of microglial polarization markers ionized calcium-binding adapter molecule 1（IBA1），inducible nitric oxide synthase（iNOS），arginase-1（ARG1）， and inflammatory cytokines in hippocampal tissue was detected by quantitative real-time PCR（qRT-PCR）. The protein expression of IBA1，iNOS，and ARG1 in the hippocampus was detected by immunofluorescence staining. [Results] Compared with the model group， the BGTLP group showed increased total distance，average speed，central time，and central distance in the open field test（P<0.05）； significantly shortened escape latency（P<0.01）；increased platform crossing times，target quadrant residence time，target quadrant time ratio and distance ratio（P<0.05）；improved cerebral blood flow perfusion（P<0.01）；alleviated hippocampal damage and Nissl body loss，with no liver or kidney injury. The levels of IL-1β，IL-6 and TNF-α were decreased（P<0.01）. The mRNA expressions of IBA1，iNOS and inflammatory factors were down-regulated，while ARG1 mRNA expression was up-regulated（P<0.05）. Immunofluorescence showed decreased expression of IBA1+ and iNOS+，increased expression of ARG1（+ P<0.05）and decreased iNOS+/ARG1+ratio（P<0.01）. [Conclusion] BGTLP may improve cognitive function in VCI rats by regulating microglial M1/M2 polarization homeostasis and alleviating neuroinflammatory responses. |
| Key words: Bagui Tianlong Powder vascular cognitive impairment microglia cell polarization neuroinflammation |
