Zhu Li, Wu Xiao-Mei, Yang Lei, Du Fang, Qian Zhong Ming
Institute for Nautical Medicine and Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, PRC.
Brain Res. 2007 Aug 29;1166:1-8. doi: 10.1016/j.brainres.2007.07.003. Epub 2007 Jul 14.
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular and systemic oxygen homeostasis. Recently, we demonstrated that ginkgolides, the main constituents of the non-flavone fraction of the standardized Ginkgo biloba (Ginkgoaceae) extract EGb 761, have a significant protective role against chemical and physical hypoxia-induced injury in neurons and PC12 cells. Based on the findings and the function of HIF-1 as a master regulator of oxygen homeostasis, we speculate that the protective role of ginkgolides might be mediated by HIF-1. In this study, we therefore investigated the effects of ginkgolides on the expression of HIF-1alpha, the cell viability and the lactate dehydrogenase (LDH) release in the hypoxic cortical neuron. We demonstrated that ginkgolides significantly increase the expression of HIF-1alpha and the cell viability as well as decrease the release of LDH in the hypoxic neuron. The findings suggested that the neuroprotective role of ginkgolides against hypoxia-induced injury might be associated with its role to up-regulate the expression of HIF-1alpha in the hypoxic neurons.
缺氧诱导因子-1（HIF-1）是细胞和全身氧稳态的主要调节因子。最近，我们证明，银杏叶标准化提取物EGb 761中非黄酮部分的主要成分银杏内酯，对化学和物理缺氧诱导的神经元及PC12细胞损伤具有显著的保护作用。基于这些发现以及HIF-1作为氧稳态主要调节因子的功能，我们推测银杏内酯的保护作用可能由HIF-1介导。因此，在本研究中，我们研究了银杏内酯对缺氧皮层神经元中HIF-1α表达、细胞活力及乳酸脱氢酶（LDH）释放的影响。我们证明，银杏内酯可显著增加缺氧神经元中HIF-1α的表达及细胞活力，并减少LDH的释放。这些发现表明，银杏内酯对缺氧诱导损伤的神经保护作用可能与其上调缺氧神经元中HIF-1α表达的作用有关。
