二氮嗪再灌注处理通过抑制细胞内ROS信号保护心肌细胞  

Diazoxide Decrease Ischemia-Reperfusion Injury by Down-Regulating Cellular ROS Signal

作　　者：苏浩[1] 杨莹莹[1] 谭文 孙晓鸥[1] Su Hao;Yang Yingying;Tan Wen;Sun Xiaoou(School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006;Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006)

机构地区：[1]华南理工大学生物科学与工程学院,广州510006 [2]广东工业大学生物医药研究院,广州510006

出　　处：《基因组学与应用生物学》2018年第6期2702-2707,共6页Genomics and Applied Biology

基　　金：国家自然科学基金青年基金(31601089);华南理工大学中央高校面上项目(2015ZM177)共同资助

摘　　要：恢复心肌血流量是目前针对急性心肌梗塞的有效治疗方式,但是在心肌再灌注过程中会进一步引起心肌细胞的坏死和调亡。二氮嗪是一种线粒体ATP敏感型钾离子通道开放剂,研究证明二氮嗪预处理具有心肌保护功能。本研究主要探讨二氮嗪再灌注处理是否具有心肌细胞保护作用并探讨其分子机制。以体外培养的H9c2心肌细胞为研究对象,通过联合缺氧模拟在体心肌缺血复灌损伤,检测细胞凋亡、线粒体膜电位、细胞内活性氧及钙离子各项指标的变化。结果发现,与正常组（control）相比,缺血再灌损伤组（ischemia-reperfusion injury,IRI）细胞活性显著下降,细胞凋亡率显著升高,线粒体跨膜电位（MMP）下降,同时细胞内活性氧（reactive oxygen species,ROS）和钙离子大量爆发,二氮嗪在这一过程中通过抑制细胞内ROS的增加、保护线粒体膜电位起到心肌细胞保护作用,并且其保护作用与细胞内另一种重要的第二信使钙离子没有直接关系。To investigate the card iac protection of diazoxide and its mechanism in ischemia-reperfusion injury,H9c2 cells were divided into 3 groups： Control, IRI, and IRI＋DZ. Cell apoptosis analysis, examination of mitochondrial membrane potential（MMP）, measurement of cellular reactive oxygen species（ROS） and cellular calcium level were performed. Results showed that the cell apoptosis ratio, cellular ROS levels, and cellular calcium concentration increased significantly after ischemia-reperfusion. The mitochondrial membrane potential showed a significant down-regulation under IRI as compared to Control group. Reperfusion with diazoxide inhibited the down-regulation of mitochondrial membrane potential and decreased IRI-induced cell apoptosis and ROS burst. But there were no significant change in cellular calcium. In summary, reperfusion with diazoxide inhibited ischemia-reperfusion injury, and this protection on H9c2 cells may be associated with ROS reduction rather than calcium signal.

关 键 词：缺血再灌注损伤 二氮嗪 活性氧 钙 

分 类 号：R965[医药卫生—药理学]