Department of Orthopedic Surgery, Fudan University Jinshan Hospital, Longhang Road, Jinshan, Shanghai 201508, China.
Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Biomed Res Int. 2020 Jun 23;2020:5939815. doi: 10.1155/2020/5939815. eCollection 2020.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). Schwann cell (SC) apoptosis contributes to the occurrence and development of DPN. Effective drugs to prevent SC apoptosis are required to relieve and reverse peripheral nerve injury caused by DM. Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], an agonist of nuclear factor erythroid derived-2-related factor 2 (Nrf2), exerts strong effect against oxidative stress in animal models or clinical patients in certain diseases, including heart failure, acute kidney injury, and liver injury. The aim of the present study was to determine the effectiveness of oltipraz in preventing SC apoptosis induced by high glucose levels. RSC96 cells pretreated with oltipraz were cultured in high-glucose medium (50 mM glucose) for 24 h, and cells cultured in medium containing 5 mM glucose were used as the control. Flow cytometry was used to evaluate the degree of apoptosis. A Cell Counting Kit-8 assay was used to assess cell viability. The mitochondrial membrane potential was assessed using JC-1 staining, and reactive oxygen species (ROS) generation was measured using 20,70-dichlorodihydrofluorescein diacetate staining. In addition, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) levels were also evaluated using the corresponding kits. Flow cytometry was subsequently used to detect apoptosis, and western blotting was used to measure the expression levels of nuclear factor erythroid derived-2-related factor 2 and NADPH quinone oxidoreductase 1. The results showed that high glucose concentration increased oxidative stress and apoptosis in RSC96 cells. Oltipraz improved cell viability and reduced apoptosis of RSC96 cells in the high glucose environment. Additionally, oltipraz exhibited a significant antioxidative effect, as shown by the decrease in MDA levels, increased SOD levels, and reduced ROS generation in RSC96 cells. The results of the present study suggest that oltipraz exhibits potential as an effective drug for treatment with DPN.
糖尿病周围神经病变（DPN）是糖尿病（DM）的常见并发症。雪旺细胞（SC）凋亡有助于 DPN 的发生和发展。需要有效的药物来预防 SC 凋亡，以缓解和逆转 DM 引起的周围神经损伤。奥替普拉[4-甲基-5-（2-吡嗪基）-1,2-二硫代-3-噻唑]是核因子红细胞衍生 2 相关因子 2（Nrf2）的激动剂，在某些疾病（包括心力衰竭、急性肾损伤和肝损伤）的动物模型或临床患者中对氧化应激具有很强的作用。本研究旨在确定奥替普拉预防高糖诱导的 SC 凋亡的效果。用奥替普拉预处理的 RSC96 细胞在高糖培养基（50 mM 葡萄糖）中培养 24 h，用含 5 mM 葡萄糖的培养基培养的细胞作为对照。用流式细胞术评估凋亡程度。用细胞计数试剂盒-8 测定细胞活力。用 JC-1 染色评估线粒体膜电位，用 20,70-二氯二氢荧光素二乙酸酯染色测定活性氧（ROS）生成。此外，还使用相应的试剂盒评估丙二醛（MDA）和超氧化物歧化酶（SOD）水平。随后用流式细胞术检测细胞凋亡，用 Western blot 测定核因子红细胞衍生 2 相关因子 2 和 NADPH 醌氧化还原酶 1 的表达水平。结果表明，高葡萄糖浓度增加了 RSC96 细胞的氧化应激和凋亡。奥替普拉改善了高糖环境中 RSC96 细胞的活力并减少了细胞凋亡。此外，奥替普拉表现出显著的抗氧化作用，表现为 MDA 水平降低、SOD 水平升高和 RSC96 细胞中 ROS 生成减少。本研究结果表明，奥替普拉具有作为治疗 DPN 的有效药物的潜力。
