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基质辅助激光解吸电离飞行时间质谱成像技术研究作为潜在降胆固醇治疗药物的小扁豆提取物引起的脂质和胆汁酸修饰。

MALDI-Mass Spectrometry Imaging to Investigate Lipid and Bile Acid Modifications Caused by Lentil Extract Used as a Potential Hypocholesterolemic Treatment.

机构信息

The Maastricht MultiModal Molecular Imaging Institute (M4I), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands.

School of Pharmacy, Chemistry unit, University of Camerino, Camerino, Italy.

出版信息

J Am Soc Mass Spectrom. 2019 Oct;30(10):2041-2050. doi: 10.1007/s13361-019-02265-9. Epub 2019 Aug 5.

Abstract

This paper reports matrix-assisted laser desorption/ionization mass spectrometry imaging to investigate systematic effects of a lentil extract treatment to lower cholesterol levels. For this purpose, mass spectrometry imaging was used to spatially investigate modifications in the lipid composition and cholesterol levels in the brain, liver, and intestines as well as bile acids in the liver and intestine of rats treated with lentil extract. Neither the lipid composition nor cholesterol levels in the brain samples were found to be significantly different between the treated and not-treated animal groups. The hypercholesterolemic livers showed signs of steatosis (lipid marker PG 36:4), but no modifications in bile acid, cholesterol, and lipid composition. We found significant differences (AUC > 0.75) in the intestines regarding bile acid and lipid composition after treatment with the lentil extract. The treated rats showed a decreased reabsorption (increased excretion) of ursodeoxycholic acid, deoxycholic acid, and chenodeoxycholic acid and an increased deconjugation of taurine-conjugated bile acids (taurochenodeoxycholic acid, taurodeoxycholic acid, taurocholic acid, and 3-keto-taurocholic acid). This indicates that the lentil extract lowers the total cholesterol level in two synergic ways: (i) it increases the excretion of bile acids; hence, new bile acids are produced in the liver from serum cholesterol and (ii) the prebiotic effect leads to free taurine which upregulates the de novo synthesis of bile acid from cholesterol while activating LDL receptors. We demonstrate here that mass spectrometry imaging is a valuable tool for a better understanding of the effects of treatments such as for the synergistic cholesterol-lowering effect of the lentil extract.

摘要

本文报道了基质辅助激光解吸/电离质谱成像技术,以研究扁豆提取物降低胆固醇水平的系统效应。为此,采用质谱成像技术对经扁豆提取物处理的大鼠大脑、肝脏和肠道中的脂质组成和胆固醇水平以及肝脏和肠道中的胆汁酸进行空间研究。未处理和处理动物组之间的大脑样本中的脂质组成或胆固醇水平均无明显差异。高胆固醇血症的肝脏出现脂肪变性(脂质标志物 PG 36:4)的迹象,但胆汁酸、胆固醇和脂质组成没有变化。在用扁豆提取物处理后,我们发现肠道中的胆汁酸和脂质组成存在显著差异(AUC > 0.75)。处理后的大鼠表现出熊去氧胆酸、脱氧胆酸和鹅去氧胆酸的重吸收减少(排泄增加),以及牛磺酸结合胆汁酸的去结合增加(牛磺鹅去氧胆酸、牛磺脱氧胆酸、牛磺酸胆酸和 3-酮牛磺酸胆酸)。这表明扁豆提取物通过两种协同方式降低总胆固醇水平:(i)它增加胆汁酸的排泄;因此,新的胆汁酸由血清胆固醇在肝脏中产生;(ii)益生菌作用导致游离牛磺酸增加,从而激活 LDL 受体上调胆固醇从头合成胆汁酸。我们在这里证明,质谱成像技术是更好地理解治疗效果的有价值的工具,例如扁豆提取物的协同降胆固醇作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/007c/6805814/e0746550077a/13361_2019_2265_Fig1_HTML.jpg

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