实验性非酒精性脂肪性肝炎大鼠肝脏脂肪酸谱的变化

Q3 Pharmacology, Toxicology and Pharmaceutics Drug Development and Registration Pub Date : 2021-12-25 DOI:10.33380/2305-2066-2021-10-4(1)-206-214
E. Shustov, A. V. Bunjat, A. Platonova, O. M. Spasenkova, N. V. Kirillova, D. Ivkin, S. Okovityi, A. N. Kimaev
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引用次数: 0

摘要

介绍。非酒精性脂肪性肝病(NAFLD)是世界上最常见的肝病。非酒精性脂肪性肝炎(Non-alcoholic steatohepatitis, NASH)是一种临床进行性NAFLD的形态学形式,在成人肝移植的原因中排名第二。游离脂肪酸(FFA)的代谢和分布在本病的发病机制中起着重要作用。大量研究已经证实,外周血中游离脂肪酸的水平与NASH的严重程度直接相关,但肝脏中脂肪酸(FA)的波动对脂肪性肝炎的影响尚不清楚。实验性非酒精性脂肪性肝炎实验动物肝脏脂肪酸谱变化的研究材料和方法。该研究以17只纯种雄性大鼠为实验对象,随机分为两组:正常组(n = 6)和对照组(n = 11)。脂肪性肝炎是通过12个月的高热量高脂肪饮食来模拟的。用脂肪酸甲酯的正己烷混合物甲醇解萃取法测定了肝脏中脂肪酸的含量。LC采用气相色谱-质谱法分离。用氘化三烷酸对定量计算进行校准。研究了饱和脂肪酸和单不饱和脂肪酸的含量、它们的醛和羟基衍生物以及甾醇的含量。结果和讨论。结果显示,脂肪性肝炎动物肝脏中游离脂肪酸含量总体下降。最显著的减少主要发生在单不饱和脂肪酸和胆固醇类。此外,研究还发现,从具有相同碳链长度的单不饱和脂肪酸前体合成单不饱和脂肪酸的关键酶Δ9-desaturase的活性显著降低,表现为肝脏中单不饱和脂肪酸的数量显著减少。在研究组之间,醛和羟基酸的水平以及甾醇的水平(除了胆固醇,其含量显著下降)没有统计学上的显著变化。因此,在高热量饮食和低动力联合引起的脂肪性肝炎大鼠的肝脏中,与健康动物相比,脂肪酸的分布和浓度发生了统计学上显著的变化。FA组成的变化可能反映了NAFLD动物肝脏的适应性和病理变化,需要进一步研究。
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Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis
Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Non-alcoholic steatohepatitis (NASH), a clinically progressive morphological form of NAFLD, ranks second in the list of reasons for liver transplantation in the adult population. In the pathogenesis of this disease, metabolism and distribution of free fatty acids (FFA) play an important role. A large number of studies have established that the level of FFA in peripheral blood directly correlates with the severity of NASH, but it is still unclear what effect fluctuations in the profile of fatty acids (FA) in the liver have in steatohepatitis.Aim. Study of changes in the profile of fatty acids in the liver of laboratory animals with experimental non-alcoholic steatohepatitis.Materials and methods. The study was carried out on 17 white outbred male rats, which were randomized into two groups – intact (n = 6) and control (steatohepatitis) (n = 11). Steatohepatitis was modeled by 12-month use of a hypercaloric high-fat diet against the background of hypodynamia. The content of fatty acids in the liver was determined in the reaction of methanolysis and extraction with a hexane mixture of their methyl esters. The LC was separated by gas chromatography-mass spectrometry. Calibration for quantitative calculation was carried out with deuterated tridecanoic acid. The content of saturated and monounsaturated higher FAs, their aldehydes and hydroxy derivatives, as well as sterols were studied.Results and discussion. A total decrease in the content of FFA in the liver of animals with steatohepatitis was revealed. The most significant decrease occurred mainly in the class of monounsaturated fatty acids and cholesterol. Also, a significant decrease in the activity of Δ9-desaturase, a key enzyme in the synthesis of monounsaturated FAs from their precursor with the same carbon chain length, was revealed, which was manifested by a significant decrease in their amount in the liver. There were no statistically significant changes in the levels of aldehydes and hydroxy acids between the study groups, as well as in the level of sterols (except for cholesterol, the content of which decreased significantly).Conclusion. Thus, in the liver of rats with steatohepatitis caused by a combination of a hypercaloric diet and hypodynamia, statistically significant changes in the profile and concentration of fatty acids were found in comparison with healthy animals. The demonstrated shifts in FA composition may reflect both adaptive and pathological changes in the liver of animals with NAFLD and require further study.
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Drug Development and Registration
Drug Development and Registration Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
1.20
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0.00%
发文量
61
审稿时长
8 weeks
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