PDF(Pubmed)
Abstract：
Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV-2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV-2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p-NF-κB, TNF-α, IL-1β, Bax, and C-caspase-3. In contrast, the expression levels of p-PI3K, p-AKT, p-GSK3β, and Bcl-2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3β signaling pathway and NF-κB pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3β/NF-κB signaling pathway.
摘要：
小胶质细胞是中枢神经系统中的常驻免疫细胞，被迅速激活以介导神经炎症和凋亡，从而加重缺血性卒中(IS)后脑组织毁伤。虽然灯盏乙素对IS有特定的治疗作用，其治疗的潜在靶点机制尚未完全阐明.在这项研究中,我们使用网络药理学探索了灯盏乙素治疗IS的潜在机制。脂多糖（LPS）用于诱导体外BV-2小胶质细胞模型，而大脑中动脉闭塞（MCAO）用于诱导体内动物模型。我们的发现表明灯盏乙素在3天促进MCAO大鼠脑血流的恢复，与MCAO组明显不同。蛋白质印迹和免疫荧光显示灯盏乙素处理BV-2小胶质细胞导致蛋白表达水平和p-NF-κB免疫阳性细胞的发生率显着降低。TNF-α,IL-1β,Bax,和C-caspase-3。相比之下,p-PI3K的表达水平，p-AKT,p-GSK3β,Bcl-2进一步增加，与LPS组明显不同。PI3K抑制剂LY294002通过抑制活化小胶质细胞的神经炎症和凋亡而具有与灯盏乙素相似的作用。在MCAO模型诱导的小胶质细胞中，3天体内PI3K/AKT/GSK3β信号通路和NF-κB通路的结果与从体外细胞获得的结果一致。这些发现表明，灯盏乙素通过减少活化的PI3K/AKT/GSK3β/NF-κB信号通路介导的小胶质神经炎症和凋亡而发挥神经保护作用。
