项目名称: 二氮嗪拮抗软骨氧化损伤的作用机制研究
项目编号: No.81460339
项目类型: 地区科学基金项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 彭磊
作者单位: 海南医学院
项目金额: 49万元
中文摘要: 骨性关节炎(OA)是种降低患者的生活质量和社会生产力的退行性关节炎,目前尚无满意的治疗效果。研究证明氧化损伤在OA的发病机制中起关键作用,故降低关节腔内活性氧(ROS)的产生,是预防及治疗OA的一个新热点。二氮嗪是一种线粒体ATP敏感性钾通道(mitoKATP通道)开放剂,其具有抗氧化作用。Mobasheri A发现人正常软骨细胞及骨关节炎软骨细胞存在KATP通道。本课题组首次证实mitoKATP通道开放剂能降低双氧水诱导的OA软骨细胞的凋亡,降低ROS的产生,逆转双氧水诱导的OA软骨细胞二型胶原的降低,初步验证开放mtioKATP通道可对抗软骨细胞氧化损伤,抑制OA的进展,本项目进一步拟在体外实验和动物实验中探索最佳浓度和最佳剂量的二氮嗪对OA的保护作用及从开放软骨细胞钾通道的角度来揭示二氮嗪抗氧化损伤的机制,为临床治疗OA提供新的治疗靶点。
中文关键词: 二氮嗪;氧化损伤;骨关节炎;抗凋亡蛋白2
英文摘要: Osteoarthritis (OA) is a degenerative arthritis, reduce the patient's quality of life and social productivity. Until now, there is no satisfactory therapeutic effect. Studies have shown oxidative damage plays a key role in the pathogenesis of OA, it is to reduce the intra-articular reactive oxygen species (ROS) generation and a new hot spot for the prevention and treatment of OA. Diazoxide is a mitochondrial ATP-sensitive potassium channel (mitoKATP channel) opener, which has antioxidant properties. Mobasheri finds out KATP channel exists in normal human articular chondrocytes and osteoarthritis chondrocytes. For the first time, our research confirmed mitoKATP channel opener to reduce hydrogen peroxide-induced OA chondrocytes apoptosis, reducing the generation of ROS, reversed OA chondrocytes hydrogen peroxide-induced decrease of type II collagen, initial validation of open mitoKATP channel can confront cartilage cells from oxidative injury and inhibiting the progress of the OA. This project intends to explore the best concentration and optimal dose in vitro and animal experiments diazoxide protective effect of OA and from the point of view of the open chondrocytes potassium channel reveals diazoxide mechanism of anti-oxidative damage and to provide new therapeutic targets for the clinical treatment of OA.
英文关键词: diazoxide;Oxidative stress;osteoarthritis;bcl-2