Su Li, Zhao Hongxia, Zhang Xiuhua, Lou Ziyang, Dong Xin
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Mol Biosyst. 2016 May 24;12(6):1831-41. doi: 10.1039/c6mb00137h.
Stroke is one of the most fatal diseases in the world, which is seriously threatening human life. Raf kinase inhibitory protein (RKIP) is involved in the regulation of several signaling pathways and is important for cell growth, proliferation, differentiation and apoptosis. In the present study, the protective effect of RKIP on stroke was investigated by the metabonomics method based on the UHPLC-Q-TOF-MS technique. TTC staining of brain tissues showed that RKIP overexpression by the lentivirus markedly reduced the necrotic area after ischemic stroke. Subsequent metabolomic profiling revealed that the protective effect of RKIP overexpression on ischemic stroke is mainly reflected in the metabolism of energy, amino acids and lipids. Several metabolites involved in purine, pyrimidine and fatty acid metabolism were identified. It was also shown that the protective effect of RKIP on ischemic stroke might be mediated by inhibiting the inflammatory response. The current study provided insight into the molecular mechanism of ischemic stroke and a reliable basis for the development of novel therapeutic targets for the treatment of ischemic stroke.
中风是世界上最致命的疾病之一，严重威胁着人类生命。拉菲激酶抑制蛋白（RKIP）参与多种信号通路的调控，对细胞生长、增殖、分化和凋亡具有重要作用。在本研究中，基于超高效液相色谱-四极杆飞行时间质谱（UHPLC-Q-TOF-MS）技术，采用代谢组学方法研究了RKIP对中风的保护作用。脑组织的TTC染色显示，慢病毒介导的RKIP过表达显著减少了缺血性中风后的坏死面积。随后的代谢组学分析表明，RKIP过表达对缺血性中风的保护作用主要体现在能量、氨基酸和脂质的代谢方面。鉴定出了几种参与嘌呤、嘧啶和脂肪酸代谢的代谢物。研究还表明，RKIP对缺血性中风的保护作用可能是通过抑制炎症反应介导的。本研究为深入了解缺血性中风的分子机制以及开发治疗缺血性中风的新型治疗靶点提供了可靠依据。
