极低密度脂蛋白受体在缺血缺氧引起的心肌损伤中的作用研究-集成技术.PDF

第 7 卷 第3期 集 成 技 术 Vol. 7 No. 3 2018年5月 JOURNAL OF INTEGRATION TECHNOLOGY May 2018 极低密度脂蛋白受体在缺血缺氧引起的 心肌损伤中的作用研究 1 2 刘志华 马晨光 1 (中国科学院深圳先进技术研究院 深圳 518055) 2 (北京予求医学研究院 北京 100022) 摘  要  缺血性心肌损伤的分子病理机制一直备受国际关注。该文应用 C57BL/6 品系的野生型(WT) 小鼠、极低密度脂蛋白(Very Low Density Lipoprotein ，VLDL)受体基因敲除(VLDLR-KO)小鼠、心脏 特异性转基因(VLDLR-TG)小鼠，通过在体及离体实验研究VLDL 受体对小鼠缺血性心肌损伤的影 响，构建生物分子网络研究VLDL 受体发挥生物学功能的关键分子及其关键信号通路。通过生物网络 的功能模块计算，发现了VLDL 受体→MAPKs、AKT、NF-κB 信号通路→心肌损伤病理表型的因果关 联性，阐明了VLDL 受体影响缺血性心肌损伤的分子机制。 关键词  极低密度脂蛋白受体；缺血性心肌损伤；缺氧缺血 中图分类号  R 394.8 文献标志码  A The Role of Very Low Density Lipoprotein Receptor in Myocardial Injury Induced by Ischemia and Hypoxia LIU Zhihua1 MA Chenguang2 1( Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China ) 2( Beijing Institute of YQ Medicine, Beijing 100022, China ) Abstract The molecular mechanism of ischemic myocardial injury is still a hot topic in the international academic circles. In this paper, C57BL/6 wild type (WT) mouse strains, very low density lipoprotein (VLDL) receptor knockout (VLDLR-KO) mice and VLDL receptor transgenic (VLDLR-TG) mice, were selected to investigate on the effect of VLDL receptor on myocardial ischemic injury in vivo and in vitro. Key molecular signaling pathways were found based on the biomolecular network analyses. A causal relationship between VLDL receptor→MAPKs, AKT, NF-κB signaling pathway and the pathological phenotype of my