Cui Yuhuan, Liu Meihong, Zuo Li, Wang Haiyan, Liu Jian
Geriatric Department, The First Affiliated Hospital of Hebei Northern University, Zhangjiakou, PR China.
Department of Oncology, the 982th Hospital of the Joint Logistics Support Unit of the Chinese People's Liberation Army, Zhangjiakou, PR China.
Immunopharmacol Immunotoxicol. 2022 Jun;44(3):400-409. doi: 10.1080/08923973.2022.2052893. Epub 2022 Mar 21.
Fraxetin has antioxidant, anti-inflammation and neuroprotective functions, however, its role in ischemic stroke is still vague. Herein, this study delves into the underlying mechanism.
Ischemia and reperfusion operation were performed to establish the cerebral stroke rat models. The brain functions were evaluated with neurological score. The brain infarcted volume in fraxetin group was measured by 2,3,5-triphenyltetrazolium chloride staining. The blood-brain barrier permeability, CD34 enrichment, and the brain water content were measured by Evans blue staining, immunofluorescence staining, and wet-dry method, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were applied to examine the levels of angiogenesis- and PI3K/Akt pathway-related factors. MTT and tube formation assays were used to measure the viability and tube formation of HUVECs.
Fraxetin decreased the brain injury-related neurological score, brain infarction, and cerebral edema and maintained blood-brain barrier permeability, whereas it promoted the angiogenesis in ischemia-damaged brain enhancing CD34 enrichment, the expressions of VEGF, Ang-1, Tie-2, and CD-31, viability of HUVECs, as well as activating the phosphorylation of PI3K and Akt. Importantly, wortmannin (a specific PI3K inhibitor) impeded the fraxetin-induced cell viability, angiogenesis, and phosphorylation of Akt and PI3K in HUVECs.
Fraxetin has protective effects on the brain ischemia-reperfusion injury and promotes angiogenesis for cerebral repair phosphorylation of PI3K and Akt.
紫铆亭具有抗氧化、抗炎和神经保护作用，然而，其在缺血性卒中中的作用仍不明确。在此，本研究深入探讨其潜在机制。
进行缺血再灌注手术以建立脑卒中大鼠模型。用神经功能评分评估脑功能。用2,3,5-三苯基四氮唑氯化物染色法测量紫铆亭组的脑梗死体积。分别用伊文思蓝染色、免疫荧光染色和干湿法测量血脑屏障通透性、CD34富集和脑含水量。应用实时定量聚合酶链反应（RT-qPCR）和蛋白质印迹法（WB）检测血管生成和PI3K/Akt通路相关因子的水平。用MTT法和管形成实验检测人脐静脉内皮细胞（HUVECs）的活力和管形成能力。
紫铆亭降低了脑损伤相关的神经功能评分、脑梗死和脑水肿，并维持了血脑屏障通透性，而促进了缺血损伤脑内的血管生成，增强了CD34富集、血管内皮生长因子（VEGF）、血管生成素-1（Ang-1）、酪氨酸激酶受体 Tie-2和血小板内皮细胞黏附分子-1（CD-31）的表达、HUVECs的活力，并激活了PI3K和Akt的磷酸化。重要的是，渥曼青霉素（一种特异性PI3K抑制剂）阻碍了紫铆亭诱导的HUVECs细胞活力、血管生成以及Akt和PI3K的磷酸化。
紫铆亭对脑缺血再灌注损伤具有保护作用，并通过PI3K和Akt的磷酸化促进血管生成以修复大脑。
