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低浓度酒精对高果糖诱导的小鼠不良心血管事件的保护作用。

The protective role of low-concentration alcohol in high-fructose induced adverse cardiovascular events in mice.

作者信息

Wu Xiaoqi, Pan Bo, Wang Ying, Liu Lingjuan, Huang Xupei, Tian Jie

机构信息

Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China.

Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.

出版信息

Biochem Biophys Res Commun. 2018 Jan 1;495(1):1403-1410. doi: 10.1016/j.bbrc.2017.11.141. Epub 2017 Nov 22.

Abstract

Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high-fructose intake.

摘要

心血管疾病仍然是一个全球性的公共卫生问题。随着果糖消费量急剧增加,已有研究表明,高果糖摄入会增加心血管疾病风险。此外,新出现的证据表明,低浓度酒精摄入可能对心血管系统具有保护作用。本研究旨在探讨低浓度酒精摄入是否能预防高果糖对小鼠心血管事件的不良影响。通过苏木精-伊红染色、超声心动图、心脏重量/体重比以及肥厚标志物心钠素(ANP)表达的结果,我们发现高果糖会导致心肌肥厚,而低浓度酒精摄入可预防心肌细胞肥厚的发生。此外,我们观察到低浓度酒精摄入可抑制高果糖诱导的线粒体肿胀。低浓度酒精降低了高果糖组升高的血糖、甘油三酯和总胆固醇水平。高果糖诱导的SIRT1和PPAR-γ低表达水平在给予低浓度酒精时显著升高。高果糖组PPAR-γ启动子区组蛋白赖氨酸9乙酰化(acH3K9)水平降低,但低浓度酒精摄入时升高。高果糖组同一区域组蛋白去乙酰化酶SIRT1的结合水平增加,而低浓度酒精可阻止结合水平升高。总体而言,我们的研究表明,低浓度酒精摄入可抑制高果糖相关的心肌肥厚、心脏线粒体损伤及糖脂代谢紊乱。此外,这些发现还为低浓度酒精治疗的组蛋白乙酰化-去乙酰化机制提供了新见解,这可能有助于预防高果糖摄入诱导的心血管疾病。

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