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针对血瘀证的脂质组学与网络药理学联合研究及其保护作用

Combined Lipidomics and Network Pharmacology Study of Protective Effects of against Blood Stasis Syndrome.

作者信息

Jin Yidian, Xie Zhiru, Li Shasha, Zeng Xiangyu, Wang Leqi, Hu Ping, Zhang Hongyang, Xiao Xue

机构信息

School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.

出版信息

Evid Based Complement Alternat Med. 2021 Mar 19;2021:5526778. doi: 10.1155/2021/5526778. eCollection 2021.

Abstract

Blood stasis syndrome (BSS) is one of the most common symptoms of cardiovascular diseases (CVDs) in traditional Chinese medicine (TCM) theory. Previous studies have identified that (Danshen) has beneficial effects on BSS, but there is no relevant research from the perspective of lipidomics to study the mechanism of Danshen against BSS since hyperlipidemia has been the widely accepted risk factor of CVDs. In this study, lipidomics technology combined with network pharmacology was applied to investigate the pathological mechanism of BSS and the protective effects of Danshen. The lipidomics profiling based on the UPLC-QTOF-MS analysis method was applied to identify the differential metabolites in the plasma of blood stasis rats. The related pathway and potential targets involved in the anti-BSS effects of Danshen were predicted by pathway analysis and network pharmacology. The biochemical results showed that Danshen intervention significantly reduced whole blood viscosity (WBV) at all the shear rates and fibrinogen concentration (FIB) ( < 0.01) and increased activated partial thromboplastin time (APTT) effectively ( < 0.01). We also found that 52 lipid metabolites, including glycerophospholipid, sphingolipid, glycerolipid, plasmalogen, cholesterol ester, and testosterone, were associated with blood stasis. Moreover, Dgka, Hsd17b3, Hsd3b1, Inppl1, Lpl, Pik3ca, Pik3r1, Pla2g1b, Pla2g2a, Soat1, and Soat2 were predicted as potential targets, while glycerophospholipid metabolism, glycerolipid metabolism, steroid and steroid hormone biosynthesis, phosphatidylinositol signaling system, and ether lipid metabolism were involved as shared critical pathways of lipidomics analysis and network pharmacology. Collectively, this study offered a new understanding of the protection mechanism of Danshen against BSS, which provided new insight to explore the protective effects of Danshen.

摘要

血瘀证是中医理论中心血管疾病(CVDs)最常见的症状之一。以往研究已证实丹参对血瘀证有有益作用,但由于高脂血症一直是被广泛认可的心血管疾病危险因素,尚无从脂质组学角度研究丹参抗血瘀证机制的相关研究。本研究应用脂质组学技术结合网络药理学来探讨血瘀证的病理机制及丹参的保护作用。基于超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF-MS)分析方法的脂质组学图谱被用于鉴定血瘀大鼠血浆中的差异代谢物。通过通路分析和网络药理学预测丹参抗血瘀证作用涉及的相关通路和潜在靶点。生化结果表明,丹参干预显著降低了所有剪切速率下的全血粘度(WBV)和纤维蛋白原浓度(FIB)(P<0.01),并有效增加了活化部分凝血活酶时间(APTT)(P<0.01)。我们还发现52种脂质代谢物,包括甘油磷脂、鞘脂、甘油脂、缩醛磷脂、胆固醇酯和睾酮,与血瘀有关。此外,预测Dgka、Hsd17b3、Hsd3b1、Inppl1、Lpl、Pik3ca、Pik3r1、Pla2g1b、Pla2g2a、Soat1和Soat2为潜在靶点,而甘油磷脂代谢、甘油脂代谢、类固醇和类固醇激素生物合成、磷脂酰肌醇信号系统以及醚脂代谢作为脂质组学分析和网络药理学的共同关键通路参与其中。总体而言,本研究为丹参抗血瘀证的保护机制提供了新的认识,为探索丹参的保护作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db9c/7997765/cc052180f271/ECAM2021-5526778.001.jpg

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