Guo Huizhen, Kong Songzhi, Chen Weimin, Dai Zhenhua, Lin Tongxiang, Su Jiyan, Li Shanshan, Xie Qingfeng, Su Ziren, Xu Yang, Lai Xiaoping
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.
Neurochem Res. 2014 Nov;39(11):2197-210. doi: 10.1007/s11064-014-1421-0. Epub 2014 Sep 11.
Ischemic stroke has been confirmed to cause neuronal injury due to its insufficient supply of glucose and oxygen to brain tissue. Previous research has shown that oxidative stress, a result of excessive accumulation of reactive oxygen species (ROS), relates to pathophysiology of ischemic stroke, and causes oxidative damage to biomolecules, eventually leading to programmed cell death. Meanwhile, apigenin has been shown to exhibit antioxidant, anti-inflammatory, anti-cancer properties and neuroprotective action. Hence, this study was to investigate the potential mechanisms underlying the neural protection of apigenin on oxygen and glucose deprivation/reperfusion (OGD/R) induced neuronal injury in differentiated PC12 cells. Cells were pretreated with apigenin for 6 h, and then subjected to OGD for 12 h followed by reperfusion for 24 h. The results showed that OGD/R significantly decreased cell viability, mitochondrial membrane potential, mRNA levels of antioxidant and detoxifying enzymes and Nrf2 protein expression, while elevated the release of LDH, cell apoptosis, intracellular ROS level, P53 protein expression and upregulated its downstream genes in PC12 cells. However, apigenin effectively inhibited these undesirable changes induced by OGD/R. Our findings demonstrate that this compound attenuates OGD/R induced neuronal injury mainly by virtue of its anti-apoptosis and antioxidative properties via affecting the expression of Nrf2 and P53, and their downstream target gene transcription.
缺血性中风已被证实会因脑组织葡萄糖和氧气供应不足而导致神经元损伤。先前的研究表明，氧化应激作为活性氧（ROS）过度积累的结果，与缺血性中风的病理生理学相关，并会对生物分子造成氧化损伤，最终导致程序性细胞死亡。同时，芹菜素已被证明具有抗氧化、抗炎、抗癌特性及神经保护作用。因此，本研究旨在探讨芹菜素对氧糖剥夺/复灌注（OGD/R）诱导的分化型PC12细胞神经元损伤进行神经保护的潜在机制。细胞先用芹菜素预处理6小时，然后进行12小时的氧糖剥夺，随后再灌注24小时。结果显示，OGD/R显著降低了PC12细胞的活力、线粒体膜电位、抗氧化和解毒酶的mRNA水平以及Nrf2蛋白表达，同时升高了乳酸脱氢酶（LDH）的释放、细胞凋亡、细胞内ROS水平、P53蛋白表达，并上调了其下游基因。然而，芹菜素有效抑制了OGD/R诱导的这些不良变化。我们的研究结果表明，该化合物主要通过影响Nrf2和P53及其下游靶基因转录的表达，凭借其抗凋亡和抗氧化特性减轻OGD/R诱导的神经元损伤。
