Department of Neurosurgery, Jingjiang People's Hospital, Jingjiang, China.
J Biochem Mol Toxicol. 2024 Dec;38(12):e70035. doi: 10.1002/jbt.70035.
Paeonol is a principle bioactive compound separated from the root bark of Cortex Moutan and has been shown to confer various biological functions, including antineuroinflammation and neuroprotection. Inflammation, blood-brain barrier (BBB), permeability, and apoptosis are three major underlying mechanisms involved in early brain injury (EBI) postsubarachnoid hemorrhage (SAH). This study aimed to detect the roles and mechanisms of paeonol in EBI following SAH. A SAH model was established by an endovascular perforation method in Sprague-Dawley rats. The localizations of HMGB1 and p65 were identified by immunofluorescence staining. Protein levels were measured by western blot analysis. The serum levels of HMGB1 and the levels of inflammatory cytokines in the brain cortex were evaluated by ELISA. Hematoxylin and eosin staining was conducted to detect neuronal degeneration. Brain water content and Evans blue extravasation were assessed to determine EBI. Neuronal apoptosis was examined by TUNEL. Paeonol deacetylated HMGB1 by upregulating SIRT1 level. SIRT1 inhibition attenuated the protective effects of paeonol against neurological dysfunctions, brain edema, and BBB disruption. SIRT1 inhibition rescued the paeonol-induced inhibition in inflammatory response. The paeonol-induced decrease in neuronal apoptosis was restored by SIRT1 inhibitor. The paeonol-mediated deactivated TLR4/MyD88/NF-κB pathway was activated by SIRT1 inhibitor. Paeonol alleviates the SAH injury in rats by upregulating SIRT1 to inactivate the HMGB1/TLR4/MyD88/NF-κB pathway.
丹皮酚是从牡丹皮中分离得到的一种主要生物活性化合物，具有多种生物学功能，包括抗神经炎症和神经保护作用。炎症、血脑屏障（BBB）通透性和细胞凋亡是蛛网膜下腔出血（SAH）后早期脑损伤（EBI）的三个主要潜在机制。本研究旨在探讨丹皮酚在 SAH 后 EBI 中的作用和机制。通过血管内穿孔方法在 Sprague-Dawley 大鼠中建立 SAH 模型。通过免疫荧光染色鉴定 HMGB1 和 p65 的定位。通过 Western blot 分析测量蛋白质水平。通过 ELISA 评估血清 HMGB1 水平和皮质炎症细胞因子水平。通过苏木精和伊红染色检测神经元变性。通过测定脑水含量和 Evans 蓝渗出评估 EBI。通过 TUNEL 检测神经元凋亡。丹皮酚通过上调 SIRT1 水平使 HMGB1 去乙酰化。SIRT1 抑制减弱了丹皮酚对神经功能障碍、脑水肿和 BBB 破坏的保护作用。SIRT1 抑制挽救了丹皮酚诱导的炎症反应抑制。SIRT1 抑制剂恢复了丹皮酚诱导的神经元凋亡减少。SIRT1 抑制剂激活了丹皮酚介导的失活 TLR4/MyD88/NF-κB 通路。丹皮酚通过上调 SIRT1 来抑制 HMGB1/TLR4/MyD88/NF-κB 通路，从而减轻大鼠的 SAH 损伤。
