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Lipid Profiling of Serum and Lipoprotein Fractions in Response to Pitavastatin Using an Animal Model of Familial Hypercholesterolemia.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-02-04 , DOI: 10.1021/acs.jproteome.9b00602
Hiroaki Takeda 1 , Yoshihiro Izumi 1 , Shohei Tamura 2 , Tomonari Koike 2 , Yui Koike 2 , Masashi Shiomi 2, 3 , Takeshi Bamba 1
Affiliation  

Statins are widely used for the treatment of atherosclerotic cardiovascular diseases. They inhibit cholesterol biosynthesis in the liver and cause pleiotropic effects, including anti-inflammatory and antioxidant effects. To develop novel therapeutic drugs, the effect of blood-borne lipid molecules on the pleiotropic effects of statins must be elucidated. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for hypercholesterolemia, are suitable for the determination of lipid molecules in the blood in response to statins because their lipoprotein metabolism is similar to that of humans. Herein, lipid molecules were investigated by lipidome analysis in response to pitavastatin using WHHLMI rabbits. Various lipid molecules in the blood were measured using a supercritical fluid chromatography triple quadrupole mass spectrometry. Cholesterol and cholesterol ester blood concentrations decreased by reducing the secretion of very low density lipoproteins from the liver. Independent of the inhibition effects of cholesterol biosynthesis, the concentrations of some lipids with anti-inflammation and antioxidant effects (phospholipid molecules with n-6 fatty acid side chains, lysophosphatidylcholines, phosphatidylethanolamine plasmalogens, and ceramide molecules) were significantly altered. These findings may lead to further investigation of the mechanism of statin action.

中文翻译:

使用家族性高胆固醇血症动物模型,对匹伐他汀产生血清和脂蛋白组分的脂质谱分析。

他汀类药物被广泛用于治疗动脉粥样硬化性心血管疾病。它们抑制肝脏中胆固醇的生物合成,并引起多效作用,包括抗炎和抗氧化作用。为了开发新的治疗药物,必须阐明血脂分子对他汀类药物的多效性作用。易患心肌梗塞的渡边遗传性高脂血症(WHHLMI)兔是高胆固醇血症的动物模型,适用于测定对他汀类药物反应的血液中的脂质分子,因为它们的脂蛋白代谢与人类相似。本文中,使用WHHLMI兔通过脂质组分析对匹伐他汀起反应,研究脂质分子。使用超临界流体色谱三重四极杆质谱仪测量血液中的各种脂质分子。胆固醇和胆固醇酯的血药浓度通过减少肝脏中极低密度脂蛋白的分泌而降低。与胆固醇生物合成的抑制作用无关,具有抗发炎和抗氧化作用的某些脂质(具有n-6个脂肪酸侧链的磷脂分子,溶血磷脂酰胆碱,磷脂酰乙醇胺缩醛磷脂和神经酰胺分子)的浓度发生了显着变化。这些发现可能导致他汀类药物作用机制的进一步研究。与胆固醇生物合成的抑制作用无关,具有抗发炎和抗氧化作用的某些脂质(具有n-6个脂肪酸侧链的磷脂分子,溶血磷脂酰胆碱,磷脂酰乙醇胺缩醛磷脂和神经酰胺分子)的浓度发生了显着变化。这些发现可能导致他汀类药物作用机制的进一步研究。与胆固醇生物合成的抑制作用无关,具有抗发炎和抗氧化作用的某些脂质(具有n-6个脂肪酸侧链的磷脂分子,溶血磷脂酰胆碱,磷脂酰乙醇胺缩醛磷脂和神经酰胺分子)的浓度发生了显着变化。这些发现可能导致他汀类药物作用机制的进一步研究。
更新日期:2020-02-04
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