Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Graduate School, Chiang Mai University, Chiang Mai, 50200, Thailand.
Neurotox Res. 2022 Feb;40(1):14-25. doi: 10.1007/s12640-021-00470-7. Epub 2022 Jan 8.
Cerebral damage following cerebral ischemia/reperfusion injury affects the neurological deficits and motor impairment of stroke patients in the long-term period. Angiogenesis, the essential process for restoration of cerebral blood flow (CBF) in the ischemic brain, promotes the recovery of neurological function following ischemia. The aim of this study was to investigate the long-term effects of morin on angiogenesis and functional outcomes in a middle cerebral artery occlusion (MCAO) and reperfusion model. Male Wistar rats were subjected to MCAO, and they were administered 30 mg/kg of morin at reperfusion via i.p. injection daily for 14 days. Fourteen days after I/R injury, the rats were evaluated for the brain damage, and angiogenic factors involved in Ang1/Tie-2 and Wnt/β-catenin signaling. In addition, at 1, 7, and 14 days after reperfusion, rotarod and pole tests were performed to investigate the functional recovery. We found morin significantly reduced the infarct size, blood-brain barrier (BBB) leakage, and apoptotic cells at 14 days after I/R injury. It also promoted angiogenesis via boosting the expression of angiogenic proteins, such as angiopoietin 1 (Ang1), Tie-2, Wnt3α, β-catenin, and cyclin D1. Morin-mediated angiogenesis was confirmed by a significant increase in microvessel's density in the penumbra area and an increase in von Willebrand factor (vWF) protein expression of the morin-treated rats. Moreover, the rotarod and pole tests also demonstrated morin increased functional recovery in the morin-treated rats compared to the vehicle rats. Therefore, our data exposed that morin promotes angiogenesis and improves functional outcomes in MCAO and reperfusion rats.
脑缺血/再灌注损伤后引起的脑损伤会影响中风患者的长期神经功能缺损和运动障碍。血管生成是缺血性大脑恢复脑血流（CBF）的必要过程，可促进缺血后神经功能的恢复。本研究旨在探讨桑色素在大脑中动脉闭塞（MCAO）和再灌注模型中对血管生成和功能结果的长期影响。雄性 Wistar 大鼠进行 MCAO 后，通过腹腔注射每天给予 30mg/kg 桑色素，再灌注 14 天。在 I/R 损伤后 14 天，评估大鼠的脑损伤和参与 Ang1/Tie-2 和 Wnt/β-catenin 信号通路的血管生成因子。此外，在再灌注后 1、7 和 14 天，进行转棒和棒试验以研究功能恢复情况。结果发现，桑色素显著降低 I/R 损伤后 14 天的梗死面积、血脑屏障（BBB）渗漏和凋亡细胞。它还通过增强血管生成蛋白（如血管生成素 1（Ang1）、Tie-2、Wnt3α、β-catenin 和细胞周期蛋白 D1）的表达来促进血管生成。桑色素介导的血管生成通过增加缺血半影区微血管密度和增加桑色素处理大鼠的血管性血友病因子（vWF）蛋白表达来证实。此外，转棒和棒试验还表明，与载体组大鼠相比，桑色素治疗组大鼠的功能恢复增加。因此，我们的数据表明，桑色素可促进 MCAO 和再灌注大鼠的血管生成并改善功能结果。
