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Relative quantification of neuronal polar lipids by UPLC-MS reveals the brain protection mechanism of Danhong injection

机译:UPLC-MS的神经元极性脂质的相对定量揭示了丹洪注射的脑保护机制

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摘要

Promising results from clinical trials have fueled a growing acceptance of Danhong injection (DHI) as a Chinese Materia Medica standardized product for the treatment of ischemic stroke. However, little information is available on the underlying mechanisms of DHI especially in lipidomics. In this study, experiments on permanent middle cerebral artery occlusion (MCAO) in mice were carried out to confirm the protective effect of DHI. Furthermore, primary mouse cortical neurons subjected to oxygen-glucose-deprivation (OGD) were used to investigate the protective mechanisms of DHI. A UPLC-MS profiling analysis for neuronal polar lipids including phosphatidylcholines (PCs), sphingomyelins (SMs) and ceramides (Cers) was carried out in order to study the potential biomarkers in this OGD-induced neuron injury model. The results showed that pretreatment with DHI resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline in MCAO mice. In an OGD-induced neuron injury model, DHI exhibited remarkable neuroprotection by reducing the neuronal damage and excessive accumulation of intracellular reactive oxygen species, suppressing intracellular free calcium influx and apoptosis. Meanwhile, 28 biomarkers of PCs, SMs and Cers sub-species of neuronal injury induced by OGD have been identified for the first time. The perturbations could be partly reversed by DHI intervention such as PC (17: 0,0: 0), PC (18: 0,0: 0), PC (16: 0,0: 0), PC (P-16: 0,0: 0) and SM (18: 0,16: 0). The results specifically provide information on the relationships between PCs, SMs, Cers sub-species and neuronal damage mechanisms during an ischemic stroke. Overall, we found that the therapeutic effects of DHI on cerebral ischemia are partially due to interferences with the PC and SM metabolisms.
机译:临床试验的有希望的结果促使对丹虹注射(DHI)作为中国本草标准化产品的促进促进,用于治疗缺血性卒中。然而,少数信息尤其是在脂类族菌中的潜在机制。在该研究中,进行了小鼠永久性脑动脉闭塞(MCAO)的实验,以确认DHI的保护作用。此外,用于进行氧血糖剥夺(OGD)的原发性小鼠皮质神经元探讨DHI的保护机制。进行了包括磷脂酰胆碱(PCS),鞘磷脂(SMS)和神经酰胺(CERS)的神经元极性脂质的UPLC-MS分析分析,以研究该OGD诱导的神经元损伤模型中的潜在生物标志物。结果表明,DHI预处理导致梗死体积明显较小,更好的神经学评数比MCAO小鼠的盐水预处理。在OGD诱导的神经元损伤模型中,通过降低细胞内反应性氧物种的神经元损伤和过度积累,DHI表现出显着的神经保护,抑制细胞内的游离钙流入和细胞凋亡。同时,首次鉴定了28个PC,SMS和CERS子宫内损伤的神经元损伤的亚物种。扰动可能部分地通过PC(17:0,0:0),PC(16:0,0:0),PC(P-16: 0,0:0)和SM(18:0,16:0)。结果具体提供了关于在缺血性卒中期间PC,SMS,CER子种类和神经元损伤机制之间的关系的信息。总体而言,我们发现DHI对脑缺血的治疗效果部分由于与PC和SM代谢的干扰。

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  • 来源
    《RSC Advances》 |2017年第72期|共11页
  • 作者单位

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    Shanxi Med Univ Dept Pharmaceut Sci 56 Xinjian South Rd Taiyuan 030001 Shanxi Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    Shanxi Med Univ Dept Pharmaceut Sci 56 Xinjian South Rd Taiyuan 030001 Shanxi Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    Beijing Omics Biol Technol Co LTD Beijing Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Dong Nei Nan Xiao Jie 16 Beijing 100700 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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