UHPLC-LTQ-Orbitrap-based metabolomics coupled with metabolomics pathway analysis method for exploring the protection mechanism of Kudiezi injection in a rat anti-ischemic cerebral reperfusion damage model
UHPLC-LTQ-Orbitrap-based metabolomics coupled with metabolomics pathway analysis method for exploring the protection mechanism of Kudiezi injection in a rat anti-ischemic cerebral reperfusion damage model
复制标题
基于UHPLC-LTQ-Orbitrap的代谢组学联合代谢组学通路分析方法探讨苦碟子注射液对大鼠抗缺血性脑再灌注损伤模型的保护机制
DOI：
10.1016/s1875-5364(18)30013-x
复制
发表时间：
2017-12-01
影响因子：
4.6
通讯作者：
Zhang Jia-Yu
中科院分区：
文献类型：
--
作者：
Liu Si-Yi;Cai Wei;Zhang Jia-Yu
苦碟子注射液已广泛应用于心脑血管疾病的治疗。然而，其治疗效果和潜在的作用机制尚不完全清楚。本研究旨在用代谢组学方法阐明苦碟子注射液对脑缺血损伤的保护作用机制。采用大脑中动脉闭塞(MCAO)方法建立大鼠脑缺血损伤模型。建立了基于UHPLC-LTQ-Orbitrap的代谢物分析方法。所有样本的原始数据用Sieve 2.2软件进行归一化处理，然后引入正交偏最小二乘判别分析(OPLS-DA)模型。最后，根据准确的质量测量(<；5ppm)、MS/MS裂解图谱和诊断产物离子，选择了血浆中的23种代谢物(15种初步鉴定)作为潜在的生物标志物。此外，在代谢组学途径分析(MetPA)代谢途径分析的基础上，首次发现苦碟子注射液抗脑缺血再灌注损伤的保护机制可能与苯丙氨酸、酪氨酸和色氨酸的生物合成有关。本研究为探讨缺血性中风的发病机制和评价苦碟子注射液等传统药物的疗效提供了一条有用的途径。
Kudiezi injection has been used extensively in the treatment of cerebrovascular and cardiovascular diseases. However, its therapeutic effects and underlying mechanism of action are not fully understood. The aim of the present study was to clarify the protective mechanisms of Kudiezi injection on cerebral ischemic injury, using metabolomics methods. Middle cerebral artery occlusion (MCAO) was introduced in rats to build the cerebral ischemic damage. UHPLC-LTQ-Orbitrap-based analytical method was established for analysis of the metabolites. The raw mass data of all samples were normalized with Sieve 2.2 software and then introduced to orthogonal partial least squares discriminant analysis (OPLS-DA) model. Finally, 23 metabolites in plasma (15 were tentatively identified) were chosen as potential biomarkers, according to accurate mass measurements (< 5 ppm), MS/MS fragmentation patterns, and diagnostic product ions. Furthermore, on the basis of metabolic pathway analysis via metabolomics pathway analysis (MetPA), we first discovered that the protection mechanism in anti-ischemic cerebral reperfusion damage of Kudiezi injection was possibly related to the biosynthesis of phenylalanine, tyrosine, and tryptophan. The present study provided a useful approach for exploring the mechanism of ischemic stroke and evaluating the efficacy of Kudiezi injection or other traditional medicines.