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机构地区:[1]河南大学医学院环境医学研究所,河南开封475004 [2]河南大学环境与健康工程中心,河南开封475004
出 处:《药学学报》2012年第9期1147-1152,共6页Acta Pharmaceutica Sinica
基 金:国家重大环保公益项目专项(200809115);省部共建河南大学科研项目(SBGJ090702)
摘 要:为了探讨亚硝酸盐对大鼠嗜铬细胞瘤细胞(PC12细胞)诱导分化能力,将PC12细胞培养在预置人工基质胶的培养板中,加入亚硝酸钠作为诱导模型。设空白对照组为阴性对照组,神经生长因子(NGF)组为阳性对照组。处理48 h后,亚硝酸钠明显增强细胞活力和血管内皮生长因子(VEGF)分泌;如同NGF效应一样,与空白对照组相比,亚硝酸钠(1.4 mmol.L 1)处理组的神经突起的PC12细胞数增多,突起的长度增加(P<0.05);VEGF mRNA表达上调(P<0.05),VEGF和缺氧诱导因子1α(HIF-1α)蛋白表达增加(P<0.05);亚硝酸钠的这些效应可以被HIF-1α特异性抑制剂YC-1阻断。结果表明,低剂量亚硝酸钠可以通过HIF-1α-VEGF途径诱导PC12细胞分化。To investigate the potential ability of the nitrite to induce neuronal differentiation of PC12 cells, cultured PC12 cells planted on matrigel in the presence or absence of sodium nitrite were employed as model, nerve growth factor (NGF) served as a positive control. After 48 h, sodium nitrite enhanced cell viability and vascular endothelial growth factor (VEGF) secretion. Same as the effect of NGF, sodium nitrite (1.4 mmol L-1) treated cultures contained a greater proportion of ceils bearing neurites and neurites were much longer than those found in negative control cultures (P 〈 0.05). Compared with the negative control, sodium nitrite (1.4 mmol'L-1) also upregulated the expression of VEGF mRNA (P 〈 0.05) and hypoxia inducible factor 1 a (HIF-1 a) or VEGF protein expression (P 〈 0.05) in cultures of PC 12 cells. On the other hand, these effects of the sodium nitrite were likely mediated by HIF-1α, since their effects were antagonized by addition of HIF-la inhibitor YC-1. Taken together, these results suggest that low doses of sodium nitrite could induce neurite outgrowth in PC 12 cells by activating the HIF-1 α-VEGF pathway.
关 键 词:亚硝酸钠 PC12细胞 分化 缺氧诱导因子1 血管内皮生长因子
分 类 号:R963[医药卫生—微生物与生化药学]
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