文章摘要
李雯, ，刘平 ，卢守四,.小檗碱通过SIRT1信号通路减轻小鼠蛛网膜下腔出血后炎症损伤[J].神经损伤功能重建,2025,(1):1-4
小檗碱通过SIRT1信号通路减轻小鼠蛛网膜下腔出血后炎症损伤
Berberine Alleviates Inflammatory Damage after Subarachnoid Hemorrhage in Mice throughthe SIRT1 Signaling Pathway
  
DOI：
中文关键词: 蛛网膜下腔出血  炎症损伤  小檗碱  小胶质细胞  沉默调节蛋白1
英文关键词: subarachnoid hemorrhage  inflammatory injury  berberine  microglia  silent mating type information regulation 2 homolog-1
基金项目:
作者单位
李雯a,c ，刘平b ，卢守四b,c 中国康复研究中心 北 京 博 爱 医 院 a. 临床试验管理办公 室，b. 研究型病房， c. 科研处 
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中文摘要:
      目的：研究小檗碱对小鼠蛛网膜下腔出血（subarachnoid hemorrhage，SAH）后早期炎症损伤的作用及 小胶质细胞活化的影响，并探讨其潜在调控机制。方法：应用C57BL/6小鼠，随机分为假手术组、模型组和 小檗碱组。构建小鼠血管内刺破SAH模型，于造模后24 h测定神经功能评分。应用脱氧核糖核苷酸末端转 移酶介导的缺口末端标记法评估各组神经细胞凋亡程度变化，应用免疫荧光染色检测小胶质细胞活动及 M1和M2型表型变化，应用酶联免疫吸附测定检测各组炎症介质包括白介素（interleukin，IL）-1β、肿瘤坏死 因子-α（tumor necrosis factor，TNF-α）变化，并应用免疫印迹技术检测沉默调节蛋白1（silent mating type information regulation 2 homolog- 1，SIRT1）信号通路激活变化。结果：与假手术组相比，SAH后24 h小鼠神经 功能障碍及神经细胞凋亡程度显著升高（P＜0.05），同时伴有炎症损伤指标明显上调，包括炎症介质表达 （P＜0.05）和M1型小胶质细胞活化（P＜0.05）。而给予小檗碱治疗能显著减轻SAH后神经功能障碍（P＜ 0.05）、神经细胞凋亡（P＜0.05）及炎症损伤（P＜0.05），同时促进小胶质细胞向M2型活化（P＜0.05）。通过免 疫印迹技术检测发现小檗碱能够诱导SIRT1信号通路表达上调（P＜0.05）。结论：小檗碱能够减轻SAH后 炎症损伤并促进小胶质细胞向M2型转化，其机制可能与激活SIRT1信号通路有关。
英文摘要:
      To investigate the effects of berberine on early inflammatory damage and microglial activation following subarachnoid hemorrhage (SAH) in mice, and to explore its underlying regulatory mechanisms. Methods: C57BL/6 mice were randomly divided into sham, SAH model, and berberine-treated groups. An endovascular perforation SAH model was established in mice, and neurological function scores were assessed 24 hours post-modeling. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to evaluate changes in neuronal apoptosis among the groups. Immunofluorescence staining was applied to detect microglial activity and phenotypic shifts towards M1 and M2 types. Enzyme-linked immunosorbent assay (ELISA) was employed to measure changes in inflammatory mediators, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α, across the groups. Western blot analysis was used to detect activation changes in the silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway. Results: Compared with the sham group, mice exhibited significantly increased neurological dysfunction and neuronal apoptosis 24 hours after SAH (P<0.05), accompanied by marked upregulation of inflammatory damage indicators, including inflammatory mediator expression (P<0.05) and M1 microglial activation (P<0.05). Berberine treatment significantly alleviated neurological dysfunction (P<0.05), neuronal apoptosis (P<0.05), and inflammatory damage (P<0.05) following SAH, while promoting microglial polarization towards the M2 phenotype (P<0.05). Western blot analysis revealed that berberine induced upregulation of SIRT1 signaling pathway expression (P< 0.05). Conclusion: Berberine can mitigate inflammatory damage and promote microglial polarization towards the M2 phenotype after SAH, potentially through activation of the SIRT1 signaling pathway.
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