School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China.
Anal Bioanal Chem. 2020 Oct;412(26):7195-7209. doi: 10.1007/s00216-020-02852-w. Epub 2020 Aug 12.
Cerebral ischemia is a common cerebrovascular disease with high mortality, and thrombolysis can cause more severe reperfusion injury. In clinical practice, Ginkgo biloba dispersible tablets combined with nimodipine have been widely used to reduce cerebral ischemia-reperfusion injury, but the mechanism has not been clearly elucidated. To explore this relationship, the change in metabolism between a sham operation group, a model group and an administration group was analyzed for the period after cerebral ischemia. Biochemical assays were used to assess injury extent and the therapeutic effects of different dosing regimens. A metabolomics method based on ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was developed to screen biomarkers in plasma of rats and analyze abnormal metabolic pathways. Using statistical analysis, corticosterone, glutamine, oleic acid, isoleucine, phenylalanine and sphingomyelin (d18:1/16:0) were screened as diagnostic biomarkers. The metabolic pathways perturbed by cerebral ischemia-reperfusion involved phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, alpha-linolenic acid metabolism, retinol metabolism, alanine, aspartate and glutamate metabolism, and glycerophospholipid metabolism. Analysis of the adjustment of biomarkers at different time points showed that the best time to evaluate the efficacy of combined administration is about 6 h after administration. Both pathological characteristics and metabolomics confirmed the better effect of the combined group than the individual groups. In this study, a non-targeted metabolomics method was developed to explore the mechanism of action of the combination of traditional Chinese and Western medicine in cerebral ischemia-reperfusion treatment, providing a theoretical basis for disease prognosis and treatment options. Graphical abstract.
脑缺血是一种常见的脑血管病，死亡率高，溶栓会引起更严重的再灌注损伤。在临床实践中，银杏叶片联合尼莫地平广泛用于减轻脑缺血再灌注损伤，但作用机制尚未阐明。为了探讨这种关系，分析了假手术组、模型组和给药组脑缺血后代谢变化。采用生化测定评估损伤程度和不同给药方案的治疗效果。建立了基于超高效液相色谱-四极杆飞行时间质谱的代谢组学方法，筛选大鼠血浆中的生物标志物并分析异常代谢途径。采用统计分析筛选出皮质酮、谷氨酰胺、油酸、异亮氨酸、苯丙氨酸和神经鞘磷脂（d18:1/16:0）作为诊断标志物。脑缺血再灌注引起的代谢途径紊乱涉及苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢、α-亚麻酸代谢、视黄醇代谢、丙氨酸、天冬氨酸和谷氨酸代谢以及甘油磷脂代谢。对不同时间点生物标志物的调整分析表明，评价联合给药疗效的最佳时间约为给药后 6 h。病理特征和代谢组学均证实联合组的效果优于单独用药组。本研究采用非靶向代谢组学方法探讨了中西药联合治疗脑缺血再灌注的作用机制，为疾病预后和治疗方案提供了理论依据。图表摘要。
