Xin W, Wei T, Chen C, Ni Y, Zhao B, Hou J
Institute of Biophysics, Academia Sinica, 15 Datun Road, Chaoyang District, Beijing 100101, People's Republic of China.
Toxicology. 2000 Aug 7;148(2-3):103-10. doi: 10.1016/s0300-483x(00)00200-6.
In this study investigation is made on whether oxidative stress produced by treatment with hydroxyl radicals can induce apoptosis in rat cerebellar granule cells. The protective effects of Ginkgo biloba extract (EGb761) and its active constituents against apoptosis are also examined. The results show that hydroxyl radicals generated by the Fenton reaction induced apoptosis in cerebellar granule cells, which was associated with the decrease in the Bcl-2 mRNA level and the increase in the protein levels of the transcription factors Fos and Jun. Moreover, hydroxyl radicals induced time-dependent lipid peroxidation in cells and caused the changes in the sulfhydryl group binding sites on the membrane proteins. Hydroxyl radicals may induce apoptosis via different signaling pathways. EGb761 attenuated these changes and its different constituents showed different effects. The total flavonoid component of EGb761 and a mixture of flavonoids and terpenes protected cerebellar granule cells from oxidative damage and apoptosis induced by hydroxyl radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids and terpenes did not show a synergistic effect in this regard.
本研究旨在探讨羟基自由基处理产生的氧化应激是否能诱导大鼠小脑颗粒细胞凋亡。同时也检测了银杏叶提取物（EGb761）及其活性成分对凋亡的保护作用。结果表明，芬顿反应产生的羟基自由基可诱导小脑颗粒细胞凋亡，这与Bcl-2 mRNA水平降低以及转录因子Fos和Jun蛋白水平升高有关。此外，羟基自由基可诱导细胞内随时间变化的脂质过氧化，并导致膜蛋白上巯基结合位点的改变。羟基自由基可能通过不同的信号通路诱导凋亡。EGb761可减轻这些变化，其不同成分表现出不同的作用。EGb761的总黄酮成分以及黄酮和萜类混合物可保护小脑颗粒细胞免受羟基自由基诱导的氧化损伤和凋亡。EGb761的总萜类成分不能预防凋亡。在这方面，黄酮和萜类未表现出协同作用。
