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基于超高效液相色谱-四极杆飞行时间质谱的丹酚酸 B 和冰片治疗脑缺血的代谢组学研究。

Metabolomics Study on the Effects of Salvianolic Acid B and Borneol for Treating Cerebral Ischemia in Rats by Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry.

机构信息

1Department of Cardiology, Xi'an No.1 Hospital, Xi'an, China.

2Department of Medical Laboratory, Xi'an No.1 Hospital, Xi'an, China.

出版信息

Rejuvenation Res. 2019 Aug;22(4):313-324. doi: 10.1089/rej.2018.2099. Epub 2018 Dec 28.

Abstract

Salviae miltiorrliza-borneol Jun-Shi coupled-herbs have been widely used for treatment of ischemia stroke. Salvianolic acid B was the most abundant and bioactive compound of Salviae miltiorrliza and used for prevention and treatment of cerebrovascular diseases. However, the scientific intension and compatible mechanism of Salvianolic acid B - borneol combination were still unknown. A metabolomics study approach based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) combined with a pathological study has been applied to study the metabolic disturbances of cerebral ischemia and evaluate the efficacies of Sal B and Sal B/borneol against cerebral ischemia in middle cerebral artery occlusion (MCAO) rats. The neuroprotection of Sal B and Sal B/borneol was reversed through the evaluation of neurological deficits, infarct volume, and neuronal apoptosis in MCAO model. The metabonomic analysis revealed that the MCAO-induced cerebral ischemia could be ameliorated by Sal B through improving the energy metabolism, lipids metabolism, inflammatory responses, and oxidant stress. Borneol could enhance the neuroprotective effects, was associated with the increased concentration of Sal B, and attenuate the function of sphingolipid metabolism pathway in cerebral ischemia rats. These findings perhaps clarify the mechanism of neuroprotective effects of treating ischemia stroke by Sal B or Sal B/borneol preliminarily through metabolomics and push the quality promotion and the composition of borneol/Sal B in secondary development of prescription.

摘要

丹参-冰片药对广泛用于缺血性脑卒中的治疗。丹酚酸 B 是丹参中含量最丰富、生物活性最强的化合物,用于预防和治疗脑血管疾病。然而,丹酚酸 B-冰片组合的科学内涵和兼容机制仍不清楚。本研究采用基于超高效液相色谱四极杆飞行时间质谱联用(UPLC-Q/TOF-MS)的代谢组学研究方法,结合病理研究,研究脑缺血的代谢紊乱,并评价丹酚酸 B 和丹酚酸 B-冰片对大脑中动脉闭塞(MCAO)大鼠脑缺血的疗效。通过评价 MCAO 模型中的神经功能缺损、梗死体积和神经元凋亡,发现丹酚酸 B 和丹酚酸 B-冰片的神经保护作用可被逆转。代谢组学分析表明,丹酚酸 B 通过改善能量代谢、脂质代谢、炎症反应和氧化应激,可改善 MCAO 诱导的脑缺血。冰片可增强神经保护作用,与丹酚酸 B 浓度的增加有关,并减轻脑缺血大鼠鞘脂代谢途径的功能。这些发现可能通过代谢组学初步阐明了丹酚酸 B 或丹酚酸 B-冰片治疗缺血性脑卒中的神经保护作用机制,并推动了处方中冰片/丹酚酸 B 的质量提升和成分研究。

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