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| 褪黑素通过Nrf-2途径抑制高铁诱导成骨细胞的凋亡 |
| Melatonin inhibits the apoptosis induced by excess iron via activation of Nrf-2 signal pathway in osteoblasts |
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| DOI：10.3969/j.issn.1006.7108.2015.08.001 |
| 中文关键词: 褪黑素 铁 成骨细胞 Nrf-2信号通路 细胞凋亡 |
| 英文关键词:Melatonin Iron Osteoblasts Nrf-2 signaling pathway Cell apoptosis |
| 基金项目:国家自然科学基金项目（81170808 ,81471094);辽宁省教育厅基金（L2013301 );沈阳市科学技术基金（F12-S77-4-47) |
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| 中文摘要: |
| 目的 探讨Nrf-2途径在褪黑素抑制高铁诱导成骨细胞凋亡中的作用。方法 用细胞贴壁法培养成骨细胞 (hFOB1. 19)后，将枸橼酸铁铵(400μmol/ L)和褪黑素（100μmol/L)加人细胞培养基，培养24 h后，Annexin V-FITC/PI流式细胞学检测细胞凋亡水平;DCFH-DA荧光探针检测细胞内ROS水平；Western blot检测凋亡相关蛋白线粒体内Bax和caspase- 3，以及Nrf-2途径相关蛋白Nrf-2和HO-1。结果 高浓度枸橼酸铁铵干预成骨细胞后，与对照组相比，细胞内ROS水平增高，枸橼酸铁铵处理后凋亡增加，凋亡相关蛋白，线粒体内Bax表达增加，caspase-3表达增加，同时，Nrf-2途径相关蛋白Nrf-2及 HO-1表达增加。而褪黑素可以进一步增加细胞内的Nrf-2及HO-1水平，同时降低细胞内ROS水平，细胞凋亡率和凋亡相关蛋白表达明显降低。结论 褪黑素可以通过Nrf-2途径抑制成骨细胞的氧化应激水平，从而降低高铁引起的成骨细胞凋亡。 |
| 英文摘要: |
| Objective To investigate the effect of melatonin on the apoptosis of hFOB1. 19 cells induced by excess iron. Methods hFOB1. 19 cells were treated with ferric ammonium citrate (400μmol/L) and melatonin (100μmol/L) for 24 h. The apoptosis rate and the level of ROS were detected using flow cytometry. Proteins associated with apoptosis like Bax and caspase-3 and associated with Nrf-2 signal pathway like Nrf-2 and HO-1 were determined using Western blotting. Results The level of ROS and apoptosis rate increased after intervention with excess iron. The levels of Bax in the mitochondria and cleaved caspase-3 in the cytosol increased. However，after the pretreatment with melatonin，the level of ROS，apoptosis rate，and expression of apoptosis associated proteins decreased，and the expression of Nrf-2 and HO-1 increased. Conclusion Melatonin inhibits the level of oxidation in osteoblasts via Nrf-2 signal pathway，resulting in the reduction of apoptosis induced by excess iron. |
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