Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
Chem Biol Interact. 2010 Jan 5;183(1):165-71. doi: 10.1016/j.cbi.2009.09.020.
Apoptosis is one of the major characteristics of delayed neuronal degeneration in neuronal injury following cerebral ischemia. Hypoxia-induced apoptosis may be co-regulated by HIF-1alpha as well as many other factors. In recent years, numerous studies concerning panaxynol (PNN) have been reported. However, whether PNN can show anti-hypoxia properties is still unknown. In this study, the protective effects of PNN on OGD-induced neuronal apoptosis and potential mechanisms were investigated. Pretreatment of the cells with PNN for 24h following exposure to OGD resulted in a significant elevation of cell survival determined by MTT assay, LDH assay, Hoechst staining and flow cytometric assessment. In addition to enhancing the expression of HIF-1alpha, PNN also normalized the caspase-3 expression/activation and increased the Bcl-2/Bax ratio. In our study, the increased level of HIF-1alpha with decreased cellular apoptosis suggested an important role for HIF-1alpha in hypoxic neurons. These results indicated that the neuroprotective effects of PNN on hypoxic neurons were at least partly due to up-regulation of HIF-1alpha and raised the possibility that PNN might reduce neurodegenerative disorders and ischemic brain diseases.
细胞凋亡是脑缺血后神经元损伤中神经元迟发性退行性变的主要特征之一。缺氧诱导的细胞凋亡可能受 HIF-1α以及许多其他因素的共同调节。近年来,已有大量关于人参炔醇(PNN)的研究报告。然而,PNN 是否具有抗缺氧特性仍不清楚。在这项研究中,研究了 PNN 对 OGD 诱导的神经元凋亡的保护作用及其潜在机制。用 MTT 测定、LDH 测定、Hoechst 染色和流式细胞术评估,发现 OGD 后用 PNN 预处理细胞 24 小时,可显著提高细胞存活率。PNN 除了增强 HIF-1α的表达外,还使 caspase-3 的表达/激活正常化,并增加了 Bcl-2/Bax 比值。在我们的研究中,HIF-1α水平升高伴随着细胞凋亡减少,这表明 HIF-1α在缺氧神经元中具有重要作用。这些结果表明,PNN 对缺氧神经元的神经保护作用至少部分归因于 HIF-1α的上调,并提出了 PNN 可能减轻神经退行性疾病和缺血性脑疾病的可能性。