Liang Hai, Chang Xin, Xia Runan, Wu Wei, Guo Hongju, Yang Miao
Department of Pharmacy, The People's Hospital of Bozhou, Bozhou, Anhui, China.
Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, China.
Evid Based Complement Alternat Med. 2022 Sep 10;2022:2131561. doi: 10.1155/2022/2131561. eCollection 2022.
Ischemic stroke is a common cause of permanent disability worldwide. Magnoflorine has been discovered to have good antioxidation, immune regulation, and cardiovascular system protection functions. However, whether magnoflorine treatment protects against cerebral ischemic stroke and the mechanism of such protection remains unknown. Here, we investigated the effect of magnoflorine on the development of ischemic stroke disorder in rats. A middle cerebral artery occlusion (MCAO) model followed by 24 h reperfusion after 90 min ischemia was used. The rats were treated with magnoflorine (10 mg/kg or 20 mg/kg) for 15 consecutive days. The neurological deficit scores, cerebral infarct volume, and brain water content were measured. The neuronal density was determined using Nissl and NeuN staining. The oxidative stress levels were determined using commercial kits. Immunofluorescence staining of LC3 and western blot assay for LC3 and p62 were used to assess autophagy. Magnoflorine treatment significantly reduced the cerebral infarct volume and brain water content and improved the neurological deficit scores in the rat MCAO model. In addition, magnoflorine ameliorated neuronal injury and neuron density in the cortex of rats. Magnoflorine also prevented oxidative damage following ischemia, reflected by the decrement of nitric oxide and malondialdehyde and the increase of glutathione (GSH) and GSH peroxidase. Moreover, the fluorescence intensity of LC3 and the ratio of LC3-II to LC3-I were remarkably downregulated in ischemic rat administration of magnoflorine. Finally, the expression levels of p62, sirtuin 1 (Sirt1), and phosphorylated-adenosine monophosphate-activated protein kinase (AMPK) were upregulated with magnoflorine. Magnoflorine attenuated the cerebral ischemia-induced neuronal damage, which was possibly associated with antioxidative stress, suppression of autophagy, and activation of the Sirt1/AMPK pathway in the rats.
缺血性中风是全球永久性残疾的常见原因。已发现木兰碱具有良好的抗氧化、免疫调节和心血管系统保护功能。然而，木兰碱治疗是否能预防脑缺血性中风及其保护机制尚不清楚。在此，我们研究了木兰碱对大鼠缺血性中风疾病发展的影响。采用大脑中动脉闭塞（MCAO）模型，缺血90分钟后再灌注24小时。大鼠连续15天接受木兰碱（10mg/kg或20mg/kg）治疗。测量神经功能缺损评分、脑梗死体积和脑含水量。使用尼氏染色和NeuN染色确定神经元密度。使用商业试剂盒测定氧化应激水平。采用LC3免疫荧光染色以及LC3和p62的蛋白质免疫印迹分析来评估自噬。木兰碱治疗显著降低了大鼠MCAO模型中的脑梗死体积和脑含水量，并改善了神经功能缺损评分。此外，木兰碱改善了大鼠皮质中的神经元损伤和神经元密度。木兰碱还预防了缺血后的氧化损伤，表现为一氧化氮和丙二醛减少以及谷胱甘肽（GSH）和谷胱甘肽过氧化物酶增加。此外，在缺血大鼠给予木兰碱后，LC3的荧光强度以及LC3-II与LC3-I的比值显著下调。最后，木兰碱上调了p62、沉默调节蛋白1（Sirt1）和磷酸化腺苷单磷酸激活蛋白激酶（AMPK）的表达水平。木兰碱减轻了脑缺血诱导的神经元损伤，这可能与大鼠的抗氧化应激、自噬抑制以及Sirt1/AMPK途径的激活有关。
