Beijing Research Institution of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Beijing Research Institution of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; Dong Pharmaceutical Research of Hunan Key Laboratory, Hunan University of Medicine, Huaihua 41800, China.
Chin J Nat Med. 2017 Dec;15(12):955-960. doi: 10.1016/S1875-5364(18)30013-X.
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.
苦参碱注射液在治疗心脑血管疾病方面应用广泛。然而，其治疗效果及作用机制尚不完全清楚。本研究采用代谢组学方法，旨在阐明苦参碱注射液对脑缺血损伤的保护机制。采用大脑中动脉闭塞（MCAO）法构建大鼠脑缺血损伤模型。建立基于 UHPLC-LTQ-Orbitrap 的分析方法，对代谢物进行分析。采用 Sieve 2.2 软件对所有样品的原始质谱数据进行归一化处理，然后引入正交偏最小二乘判别分析（OPLS-DA）模型。最后，根据精确质量测量（<5 ppm）、MS/MS 碎片模式和诊断产物离子，从血浆中选择了 23 种（15 种为暂定）代谢物作为潜在的生物标志物。此外，通过代谢组学途径分析（MetPA）对代谢途径进行分析，我们首次发现苦参碱注射液抗缺血性脑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。本研究为探索缺血性脑卒中的发病机制及评价苦参碱注射液或其他中药的疗效提供了一种有效的方法。
