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| 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 mitigates neuroinflammation after subarachnoid hemorrhage in mice via modulation of sirtuin 1-dependent pathway |
| 投稿时间：2023-01-14 修订日期：2023-01-14 |
| 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 SIRT1. |
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| 中文摘要: |
| 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、SAH组和小檗碱干预组。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: |
| Abstract Objective To study the influence of berberine on the acute inflammatory response and microglia activation after experimental subarachnoid hemorrhage (SAH) in mice and to illustrate the underlying molecular mechanisms. Methods C57BL/6 mice were randomly divided into the following groups: sham group, SAH group and berberine plus SAH group. The intravascular puncture SAH mice model was established. Neurological scores were evaluated at 24 h after surgery. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to analyze neural apoptosis. The double immunofluorescence staining was used to evaluate M1 microglia and M2 microglia activation after SAH. The proinflammatory cytokines including interleukin-1β(IL-1β) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immuno sorbent assay (ELISA). The activation of silent mating type information regulation 2 homolog- 1 (SIRT1) signaling pathway was evaluated by western blotting. Results As compared with the sham-operated group, SAH significantly exacerbated neurological impairment (P < 0.05) and neural apoptosis (P < 0.05). In addition, SAH markedly induced inflammatory insults including the increased proinflammatory cytokines (P < 0.05) and M1 microglia activation (P < 0.05). In contrast, berberine treatment evidently mitigated neurological impairment (P < 0.05), neural apoptosis (P < 0.05), and inflammatory insults (P < 0.05), and further promoted M2 microglia activation (P < 0.05) when compared with SAH group. Mechanistically, berberine significantly increased SIRT1-mediated signaling pathway (P < 0.05). Conclusion Berberine could reduce neuroinflammation and promote M2 microglia activation after SAH by modulation of SIRT1-dependent signaling pathway. |
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