Wang Kaihua, Chen Zhenzhen, Huang Jianmin, Huang Longjian, Luo Ning, Liang Xiulin, Liang Mingkun, Xie Wei
Southern Medical University, Guangzhou, China.
Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.
Clin Exp Pharmacol Physiol. 2017 Aug;44(8):862-871. doi: 10.1111/1440-1681.12775.
Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischaemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague-Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups. MTT and RT-PCR were used for cell proliferation and apoptosis-related proteins analyses. The effects of NAR on the Nrf2 signalling pathway were investigated using transfection approaches. Differences in mitochondrial dysfunction were analyzed by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed and recorded; apoptosis was measured based on the TUNEL assay. Additionally, biochemical indices were detected both in vitro and in vivo. NAR promoted cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological defects, and reduce apoptosis and oxidative stress (P<.05). These findings demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2 signalling pathway is involved in this regulatory process. NAR has health-promoting properties because of its anti-apoptotic and anti-oxidant effects in cases of ischaemic stroke.
细胞凋亡和氧化应激被认为是与许多缺血性脑血管疾病的发生和发展相关的主要因素。柚皮素（NAR）是柑橘类植物中一种丰富的黄酮类化合物，已被发现具有抗氧化、抗癌和抗细胞凋亡作用。本研究旨在探讨柚皮素对缺血性中风的抗细胞凋亡和抗氧化作用。在体外，将从新生Sprague-Dawley大鼠大脑中分离的皮质神经元细胞随机分为对照组、氧糖剥夺/复灌注（OGD/Rep）组、NAR-L组、NAR-M组和NAR-H组。采用MTT法和RT-PCR法进行细胞增殖和凋亡相关蛋白分析。采用转染方法研究NAR对Nrf2信号通路的影响。通过流式细胞术分析线粒体功能障碍的差异。在体内，制备大脑中动脉闭塞（MCAO）模型，评估并记录神经功能缺损和脑湿/干（W/D）比值；基于TUNEL法检测细胞凋亡。此外，在体外和体内均检测生化指标。NAR促进皮质神经元细胞增殖，抑制细胞凋亡和氧化应激，并调节Nrf2蛋白的定位（P<0.05）。此外，Nrf2的沉默和过表达影响皮质神经元细胞的增殖和凋亡（P<0.05）。在体内，NAR可减轻脑水肿，改善神经功能缺损，并减少细胞凋亡和氧化应激（P<0.05）。这些结果表明，NAR可减少细胞凋亡和氧化应激，且Nrf2信号通路参与了这一调节过程。由于NAR在缺血性中风病例中具有抗细胞凋亡和抗氧化作用，因此具有促进健康的特性。
