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淫羊藿苷抑制甲醛诱导SH-SY5Y细胞损伤的作用及机制研究

Icariin protects SH-SY5Y cells from formaldehyde-induced injury through inhibition of tau phosphorylation

中文摘要英文摘要

背景:甲醛可损伤神经细胞,与阿尔茨海默病的发病具有密切联系。淫羊藿苷是中药淫羊藿中的一个黄酮成分,具有较好的神经保护作用,然而淫羊藿苷是否可以拮抗甲醛引起的神经损伤尚不清楚。目的:观察甲醛对人骨髓神经母细胞瘤细胞株(SH-SY5Y)的影响,观察淫羊藿苷对甲醛所致SH-SY5Y细胞损伤的影响,研究其拮抗甲醛毒性的作用及可能的作用机制。方法:将细胞分为正常对照组、甲醛损伤组和淫羊藿苷治疗组,采用CCK-8法观察各组细胞活力,采用激光共聚焦显微镜观察各组细胞形态的变化,采用流式细胞仪观察各组细胞凋亡的变化,应用Western blot蛋白分析方法研究各组tau蛋白磷酸化的变化。结果 0.3mM浓度的甲醛可造成细胞半数致死,1μM、2.5μM、5μM、10μM的ICA均可不同程度的挽救甲醛诱导的细胞损伤,其中5μM作用最佳,20μM的ICA无效。激光共聚焦显微镜结果显示5μM 的ICA可以明显拮抗甲醛对细胞形态的损伤,流式细胞仪检测结果显示ICA抑制甲醛诱导的细胞凋亡。Western blot结果显示ICA可抑制甲醛诱导的tau蛋白181、396位点的磷酸化,但是对总tau蛋白含量变化无影响,其中tau磷酸化的GSK3β促进位点Tyr216受到抑制,抑制位点S9表现出增加。结论 ICA可以有效抑制甲醛诱导的tau蛋白磷酸化,从而减轻甲醛对SH-SY5Y细胞的损伤,其通路可能是通过抑制GSK-3β介导的tau蛋白磷酸化实现的。

BACKGROUND: Formaldehyde-induced neurotoxicity is implicated in the pathology of Alzheimer's disease. Icariin, a flavonoid found in Chinese herbal medicine Epimedium, exhibits neuroprotective activity; however, whether Icariin antagonizes formaldehyde-induced nerve injury is unclear. AIMS: To investigate the neuroprotective effects of Icariin on formaldehyde-treated SH-SY5Y cells and the possible mechanisms involved. METHODS: SH-SY5Y cells were divided into control group, formaldehyde treatment group, and Icariin treatment group. Cell viability, apoptosis, and morphological changes were determined by CCK8, flow cytometry, and confocal microscopy, respectively. The phosphorylation of protein tau was examined by Western blot. RESULTS: Formaldehyde showed a half lethal dose (LD50) of 0.3 mM in SH-SY5Y cells. Icariin (1 - 10 μM) prevented formaldehyde-induced cell death in SH-SY5Y cells in a dose-dependent manner, with the optimal effect observed at 5 μM. Examination of cell morphology by confocal microscopy demonstrated that 5 μM ICA significantly attenuated formaldehyde-induced cell injury. Additionally, Icariin inhibited formaldehyde-induced cell apoptosis in SH-SY5Y cells. Results from western blot analysis showed that Icariin suppressed formaldehyde-induced tau phosphorylation at Thr181 and Ser396, while having no effect on the total tau protein level. Furthermore, Icariin reduced Tyr216 phosphorylation and increased Ser9 phosphorylation of the tau kinase GSK-3β. CONCLUTION: Icariin protects SH-SY5Y cells from formaldehyde-induced injury possibly through inhibition of GSK-3β-mediated tau phosphorylation.?????

赫荣乔、宋宜祥、王学美、黎巍威、苗君叶、强敏

神经病学、精神病学基础医学药学

淫羊藿苷甲醛tau蛋白磷酸化GSK-3β神经保护作用

Icariinformaldehydephosphorylation of protein tauGSK-3βneuroprotection

赫荣乔,宋宜祥,王学美,黎巍威,苗君叶,强敏.淫羊藿苷抑制甲醛诱导SH-SY5Y细胞损伤的作用及机制研究[EB/OL].(2014-03-27)[2025-08-23].http://www.paper.edu.cn/releasepaper/content/201403-782.点此复制

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