| 摘要: |
| [目的] 探讨川芎（CR）调控磷酸肌醇3-激酶/蛋白激酶B/转录因子叉头盒O1（PI3K/AKT/FOXO1）信号轴在修复缺血性脑卒中血管内皮损伤中的机制。[方法] 人脑微血管内皮细胞（HBMEC）分为以下4组：空白组（Con组）、氧糖剥夺/复氧组（OGD/R组）、CR组和CR+LY294002组。除Con组外，其余各组均构建OGD/R细胞模型。通过流式细胞术检测细胞凋亡，Transwell检测细胞迁移能力和试管形成试验评估细胞形成管的能力。将45只小鼠随机分为假手术组（Sham组）、大脑中动脉闭塞组（MCAO组）、MCAO+CR组，每组15只。除Sham组，其他组建立小鼠MCAO模型。通过氯化三苯基四氮唑（TTC）染色分析梗死面积，免疫荧光分析梗死组织CD31和PI3K分布，蛋白质印迹分析PI3K/AKT/FOXO1信号表达。[结果] 与Con组相比，OGD/R组HBMEC凋亡率显著增加（P<0.05），迁移细胞数与管形成数显著降低（P<0.05）。与OGD/R组相比，CR组HBMEC凋亡率显著降低（P<0.05），细胞迁移数、管形成数和p-PI3K/PI3K、p-AKT/AKT、p-FOXO1/FOXO1表达显著增加（P<0.05）。CR+LY294002组HBMEC凋亡率较CR组显著增加（P<0.05），细胞迁移数和管形成数较CR组显著降低（P<0.05）。与Sham组相比，MCAO组脑梗死面积，神经功能缺损评分显著增加（P<0.05）。与MCAO组相比，MCAO+CR组脑梗死面积，神经功能缺损评分显著降低（P<0.05）。MCAO+CR组梗死脑组织中CD31+PI3K+细胞比例和p-PI3K/PI3K、p-AKT/AKT、p-FOXO1/FOXO1表达较MCAO组显著增加（P<0.05）。[结论] CR水提物可通过激活PI3K/AKT/FOXO1信号通路，抑制缺血性损伤诱导的血管内皮细胞凋亡，促进血管生成，进而发挥缺血性脑卒中神经保护作用。 |
| 关键词: 川芎 缺血性脑卒中 小鼠 血管生成 人脑微血管内皮细胞 |
| DOI：10.11656/j.issn.1673-9043.2026.09.07 |
| 分类号:R743.3 |
| 基金项目:宁夏自然科学基金项目（2021AAC03412）。 |
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| Mechanism of Chuanxiong rhizoma regulating PI3K/AKT/FOXO1 signal axis in repairing vascular endothelial injury after ischemic stroke |
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NING Ning1, DU Xiaojuan2, LI Yunyun1, XUE Shengwen1, MA Jing1
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1.Neurology Center, 942 Hospital of Joint Logistics Support force of Chinese People's Liberation Army, Yinchuan 750000, China;2.Department of Gastroenterology, 942 Hospital of Joint Logistics Support force of Chinese People's Liberation Army, Yinchuan 750000, China
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| Abstract: |
| [Objective] To explore the mechanism of Chuanxiong Rhizoma（CR） regulating phosphoinositide 3-kinase/protein kinase B/forkhead box O1（PI3K/AKT/FOXO1） signal axis in repairing vascular endothelial injury after ischemic stroke. [Methods] Human brain microvascular endothelial cells（HBMEC） were divided into the following four groups：blank（Con） group，oxygen-glucose deprivation/reoxygenation（OGD/R） group，CR group and CR+LY294002 group. Except Con group，other groups established OGD/R model. Except Con group，other groups established OGD/R model. Apoptosis was detected by flow cytometry，cell migration ability was detected by Transwell，and the ability of cells to form tubes was evaluated by tube formation test. 45 mice were randomly divided into Sham group，middle cerebral artery occlusion（MCAO） group and MCAO+CR group，with 15 mice in each group. Except Sham group，other groups established mouse MCAO models. The infarct area was analyzed by triphenyltetrazolium chloride（TTC） staining，the distribution of CD31 and PI3K in infarcted tissues was analyzed by immunofluorescence，and the signal expression of PI3K/AKT/FOXO1 was analyzed by protein blot. [Results] Compared with Con group，the number of apoptotic cells in HBMEC in OGD/R group increased significantly（P<0.05），and the number of cell migration and tube formation decreased significantly（P<0.05）. Compared with OGD/R group，the number of apoptotic cells in HBMEC in CR group decreased significantly（P<0.05），while the number of cell migration，the number of tube formation and the expression of p-PI3K/PI3K，p-AKT/AKT，p-FOXO1/FOXO1 increased significantly（P<0.05）. The number of apoptotic cells in HBMEC in CR+LY294002 group was higher than that in CR group（P<0.05），and the number of cell migration and tube formation was lower than that in CR group（P<0.05）. Compared with Sham group，cerebral infarction area and neurological deficit score in MCAO group increased significantly（P<0.05）. Compared with MCAO group，the cerebral infarction area and neurological deficit score in MCAO+CR group decreased significantly（P<0.05）. The ratio of CD31+PI3K+ cells and the expressions of p-PI3K/PI3K，p-AKT/AKT and p-FOXO1/FOXO1 in MCAO+CR group were higher than those in MCAO group（P<0.05）. [Conclusion] CR aqueous extract inhibits apoptosis and stimulates angiogenesis in OGD/R-stimulated HBMECs and MCAO-induced mice through modulating PI3K-AKT-FOXO1 signalling. |
| Key words: Chuanxiong Rhizoma ischemic stroke mice angiogenesis human brain microvascular endothelial cells |
