Nifedipine inhibits oxidative stress and ameliorates osteoarthritis by activating the nuclear factor erythroid-2-related factor 2 pathway
Nifedipine inhibits oxidative stress and ameliorates osteoarthritis by activating the nuclear factor erythroid-2-related factor 2 pathway
复制标题
硝苯地平通过激活核因子 erythroid-2 相关因子 2 通路抑制氧化应激并改善骨关节炎
DOI：
10.1016/j.lfs.2020.117292
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发表时间：
2020-07-15
期刊：
影响因子：
6.1
通讯作者：
Li, Jia
中科院分区：
文献类型：
--
作者：
Yao, Jun;Long, Huiping;Li, Jia
硝苯地平是一种电压门控钙通道抑制剂，广泛用于治疗高血压。据报道，硝苯地平具有抗氧化和抗凋亡作用，并促进细胞增殖。然而，硝苯地平对骨关节炎（OA）软骨细胞氧化应激和细胞凋亡的影响仍不清楚。在本研究中，我们试图探讨硝苯地平是否通过核因子红细胞 2 相关因子 2 (Nrf2) 激活减轻 OA 的氧化应激和细胞凋亡。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 试剂盒检测硝苯地平对人软骨细胞的细胞毒性，并分别使用逆转录聚合酶链反应 (RT-PCR) 和蛋白质印迹法测量 mRNA 和蛋白质表达水平。通过测量活性氧（ROS）、谷胱甘肽过氧化物酶（GSH-px）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性来分析氧化应激水平。使用 Nrf2 抑制剂 brusatol (BR) 分析 Nrf2 在硝苯地平对 OA 的作用中的作用。结果显示，硝苯地平抑制基质金属蛋白（MMP）-13、白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α、环氧合酶（COX）-2、诱导型一氧化氮（NO）合酶（iNOS）和前列腺素E2（PGE2）的表达，以及 人 OA 软骨细胞中 ROS 产生减少，BR 部分逆转了这一情况。硝苯地平可防止软骨退化并促进软骨细胞中 Nrf-2 的表达。这些结果表明硝苯地平通过激活 Nrf-2/HO-1 信号传导抑制软骨细胞的炎症和氧化应激。
Nifedipine is a voltage-gated calcium channel inhibitor widely used in the treatment of hypertension. Nifedipine has been reported to have antioxidant and anti-apoptotic effects and promotes cell proliferation. However, the effects of nifedipine on oxidative stress and apoptosis in osteoarthritic (OA) chondrocytes are still unclear. In this study, we sought to investigate whether nifedipine alleviates oxidative stress and apoptosis in OA through nuclear factor erythroid-2-related factor 2 (Nrf2) activation. The cytotoxicity of nifedipine against human chondrocytes was detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) kit, whereas mRNA and protein expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The oxidative stress level was analyzed by measuring reactive oxygen species (ROS), glutathione peroxidase (GSH-px), catalase (CAT) and superoxide dismutase (SOD) activities. The role of Nrf2 in the effect of nifedipine on OA was analyzed using an Nrf2 inhibitor brusatol (BR). The result showed that nifedipine inhibited the expression of matrix metalloprotein(MMP)-13, interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, inducible nitric oxide (NO) synthase (iNOS), and prostaglandin E2 (PGE2), as well as reduced ROS production in human OA chondrocytes, which was partially reversed by BR. Nifedipine prevented cartilage degeneration and contributed to the expression of Nrf-2 in chondrocytes. These results indicate that nifedipine inhibited inflammation and oxidative stress in chondrocytes via activation of Nrf-2/HO-1 signaling.