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[他汀类药物的作用:激活脂解作用以及胰岛素依赖细胞对极低密度脂蛋白的吸收,增加多不饱和脂肪酸的生物利用度并降低低密度脂蛋白胆固醇]

[THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

作者信息

Titov V N, Malyshev P P, Amelyushkina V A, Aripovsky A V, Smirnov G P, Polevaya T Yu, Kabo S I, Kukhartchuk V V

出版信息

Klin Lab Diagn. 2015 Oct;60(10):4-12.

Abstract

The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and biological pleiotropic effect of essential polyenoic fatty acids. According our opinion, atherosclerosis is intracellular deficiency of polyenoic fatty acids. The value of cholesterol alcohol-lipoproteins of low density is equimolar to content of lipoproteins of low density in blood which under low bio-availability can't to absorb cells byforce of apoB-100-endocytosis.

摘要

俄罗斯卫生部下属的俄罗斯心脏病学研发生产联合体,俄罗斯莫斯科121552 他汀类药物是动物细胞所没有的合成异生素。它们不太可能产生多效性作用。分阶段评估他汀类药物的作用是可行的:a)最初对胆固醇醇合成的特异性抑制;b)进一步间接激活极低密度脂蛋白中甘油三酯的水解;c)非特异性激活细胞对极低密度棕榈酸和油酸脂蛋白的受体吸收,然后d)对低密度亚油酸和亚麻酸脂蛋白以及所有多不饱和脂肪酸的吸收。总体而言,他汀类药物可激活细胞对多不饱和脂肪酸的吸收。正是它们表现出了生理上的、特异性的多效性作用。他汀类药物抑制在极低密度脂蛋白中位于磷脂酰胆碱之间的胆固醇醇-脂蛋白池的合成,这些极低密度脂蛋白在甘油三酯表面的极性单层磷脂酰胆碱+胆固醇醇中浓缩。单层的低渗透性将极低密度脂蛋白中的底物甘油三酯与亲水性血浆中的肝素后脂蛋白脂肪酶分隔开。极低密度脂蛋白单层中胆固醇醇/磷脂酰胆碱的比例越高,脂解作用、极低密度配体脂蛋白的形成以及它们在载脂蛋白B-100内吞作用下被细胞吸收的速度就越慢。他汀类药物通过a)激活胰岛素依赖细胞对极低密度脂蛋白的吸收以及b)激活所有细胞对低密度脂蛋白的吸收、增加多不饱和脂肪酸的生物利用度、激活载脂蛋白B-100内吞作用来使高脂血症正常化。食物中棕榈酸饱和脂肪酸含量的限制以及ω-3多不饱和脂肪酸含量的增加可提高多不饱和脂肪酸的“生物利用度”及其被细胞的吸收,同时还可降低胆固醇醇/磷脂酰胆碱以及必需多不饱和脂肪酸的生物学多效性作用。我们认为,动脉粥样硬化是细胞内多不饱和脂肪酸的缺乏。低密度胆固醇醇-脂蛋白的价值与血液中低密度脂蛋白的含量等摩尔,在生物利用度低的情况下,其无法通过载脂蛋白B-100内吞作用被细胞吸收。

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