啤酒花经抗氧化途径减轻Aβ损伤成骨细胞作用研究
投稿时间:2021-03-17  修订日期:2021-06-01  点此下载全文
引用本文:夏天爽,刘晓燕,蒋益萍,李晓瑾,王果平,辛海量.啤酒花经抗氧化途径减轻Aβ损伤成骨细胞作用研究[J].药学实践杂志,2021,39(6):509~514
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作者单位E-mail
夏天爽 海军军医大学药学系生药学教研室上海 200433  
刘晓燕 海军军医大学药学系生药学教研室上海 200433  
蒋益萍 海军军医大学药学系生药学教研室上海 200433  
李晓瑾 新疆维吾尔自治区中药民族药研究所新疆 乌鲁木齐 830002  
王果平 新疆维吾尔自治区中药民族药研究所新疆 乌鲁木齐 830002  
辛海量 海军军医大学药学系生药学教研室上海 200433 hailiangxin@163.com 
基金项目:国家自然科学基金(82174079,U1603283,82004015),上海市科技支撑专项课题(21S21902600)
中文摘要:目的 探讨啤酒花改善β-淀粉样蛋白(Aβ)损伤成骨细胞的骨形成作用及其机制。方法 以新生24 h Wistar大鼠所分离的成骨细胞为研究对象,用Aβ1-42寡聚体对成骨细胞进行损伤,并用啤酒花提取物进行药物干预。分别采用MTT法、碱性磷酸酶(ALP)活性检测以及茜素红染色法评价成骨细胞的增殖、分化及骨矿化水平,流式细胞仪检测成骨细胞凋亡。采用蛋白质印迹法检测骨形成相关蛋白及氧化应激Nrf2、FoxO1通路蛋白的表达水平,并用免疫荧光检测FoxO1蛋白的入核表达。结果 啤酒花提取物可显著促进Aβ损伤成骨细胞的增殖,提高ALP活性及骨矿化结节水平,抑制细胞凋亡率,并促进骨形成相关蛋白I型胶原酶(COL-I)及骨桥蛋白(OPN)的表达。此外,啤酒花提取物可显著激活Aβ损伤成骨细胞的Nrf2和FoxO1信号通路,促进该氧化应激信号通路相关蛋白的表达,通过抗氧化维持骨代谢平衡。结论 本研究表明啤酒花具有减轻Aβ损伤成骨细胞的作用,初步阐明其作用机制与抗氧化有关,为抗骨质疏松作用机制及药物研发提供了新思路。
中文关键词:啤酒花  β-淀粉样蛋白  成骨细胞  抗氧化  骨质疏松
 
Hops extract alleviates Aβ-injury to osteoblasts through antioxidant pathway
Abstract:Objective To explore the effects of Humulus lupulus L. extract (HLE) and its mechanism on improving bone formation of Aβ-injured osteoblasts.Methods Osteoblasts isolated from 24 h-old Wistar rats were injured by Aβ1-42 oligomer and intervened with HLE. The proliferation, differentiation and bone mineralization of osteoblasts were determined by MTT assay, alkaline phosphatase (ALP) activity assay and alizarin red staining, respectively. The apoptosis of osteoblasts was detected by flow cytometer. The expression levels of bone formation related proteins, and proteins of Nrf2 and FoxO1 pathways were measured by Western blotting analysis. The intranuclear expression of FoxO1 protein was detected by immunofluorescence.Results HLE significantly improved the cell proliferation, ALP activity and bone mineralization, and inhibited the apoptosis of Aβ-injured osteoblasts. HLE also significantly promoted the expressions of collagen type Ι (COL-I) and osteopontin (OPN) in Aβ-injured osteoblasts. HLE notably activated the Nrf2 and FoxO1 signaling pathways in Aβ-injured osteoblasts by promoting the expressions of related proteins and maintained bone metabolism through relieving oxidative stress.Conclusion This study confirms that HLE can alleviate Aβ-injury to osteoblasts, and preliminarily clarifies the mechanism being related to antioxidation, which provides a new reference for the mechanism research and drugs development for anti-osteoporosis.
keywords:Hops (Humulus lupulus L.)    osteoblast  antioxidation  osteoporosis
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