A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption-Alcoholic Cardiomyopathy.

A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption-Alcoholic Cardiomyopathy.
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DOI:
10.3390/molecules26082177
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发表时间:
2021-04-09
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Guan D
Guan D
中科院分区:
其他
文献类型:
--
作者:
Cao Z;Wang T;Xia W;Zhu B;Tian M;Zhao R;Guan D

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慢性饮酒导致心肌损伤、心室扩张和心功能障碍,这被定义为酒精性心肌病(ACM)。为探讨ACM诱导心肌损伤及其机制,采用liberi - decarli液体日粮建立ACM动物模型,并采用组织病理学、超声心动图、分子生物学、代谢组学等方法进行研究。苏木精-伊红和马松三色染色显示ACM组心肌结构紊乱和局部纤维化。超声心动图显示,ACM组左心室壁变薄、扩张,心功能下降,血清脑利钠肽(BNP)水平和心肌BNP mRNA表达分别通过酶联免疫吸附法和实时定量聚合酶链反应(PCR)升高。通过对心肌标本的代谢组学分析,鉴定出297种差异表达代谢物,这些代谢物参与了与不饱和脂肪酸生物合成、维生素消化吸收、氧化磷酸化、戊糖磷酸、嘌呤和嘧啶代谢相关的KEGG通路。目前的研究表明,长期饮酒导致心肌细胞结构紊乱,左心室变薄和扩张,心功能下降。心肌标本的代谢组学分析和KEGG富集分析进一步表明,ACM组参与了几种差异表达的代谢物和途径,这提示了慢性酒精暴露引起心肌损伤的潜在原因,并为进一步研究阐明ACM的潜在机制提供了见解。
Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson’s trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.
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