Effects of scoparone on non-alcoholic fatty liver disease revealed by RNA sequencing.

Effects of scoparone on non-alcoholic fatty liver disease revealed by RNA sequencing.
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肩op骨对RNA测序揭示的非酒精性脂肪肝疾病的影响。

DOI:
10.3389/fendo.2022.1004284
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发表时间:
2022
影响因子:
5.2
通讯作者:
Zhang, Kefeng
Zhang, Kefeng
中科院分区:
医学2区
文献类型:
--
作者:
Huang, Xiaoyan;Gao, Ya;Cao, Houkang;Li, Jun;Mo, Siyi;Li, Ting;Wu, Jianzhao;Guo, Kai;Wei, Riming;Zhang, Kefeng

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滨蒿内酯(SCO)被认为具有减轻肝损伤的疗效。本研究的目的是通过体内实验和RNA测序观察SCO对高脂饮食(HFD)诱导的非酒精性肝病(NAFLD)的治疗作用及其可能机制。雄性昆明种小鼠灌胃高脂饲料8周,建立非酒精性脂肪性肝病小鼠模型,并用五味地黄汤治疗。采用组织病理学和生化指标评价肝损伤程度及超氧化物歧化酶的疗效。RNA测序分析阐明了SCO的保肝作用机制。最后,通过实时定量聚合酶链式反应(qRT-PCR)和免疫印迹对胆固醇合成途径和脂肪酸(甘油三酯)合成途径的差异表达基因进行验证。组织病理学结果显示,HFD可引起小鼠明显的脂肪变性,而SCO可显著减轻NAFLD小鼠的肝脏脂肪变性。生化指标测定结果表明,SCO可抑制HFD所致小鼠血清转氨酶活性升高和肝脂水平升高。肝组织的RNA测序分析发现,HFD和SCO分别显著改变了2742和3663个基因。SCO逆转了HFD诱导的胆固醇合成和脂肪酸(甘油三酯)代谢相关的大部分基因。验证实验的结果与RNA测序结果基本一致。SCO减轻NAFLD小鼠肝损伤和脂肪变性,可能与调节胆固醇和脂肪酸(甘油三酯)代谢密切相关。
Scoparone (SCO) is known to have curative effect of alleviating liver injury. The purpose of this study was to observe the therapeutic effect and possible mechanism of SCO against high-fat diet (HFD) induced non-alcoholic liver disease (NAFLD) through in vivo experiments and RNA sequencing. Male Kunming mice were fed with HFD for 8 weeks to establish a mouse model of NAFLD, and SCO was used to treat NAFLD. Histopathology and biochemical indicators were used to evaluate the liver injury and the efficacy of SCO. RNA sequencing analysis was performed to elucidate the hepatoprotective mechanism of SCO. Finally, the differentially expressed genes of cholesterol synthesis and fatty acid (triglyceride) synthesis pathways were verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The histopathological results showed that HFD could lead to significant steatosis in mice, while SCO could alleviate liver steatosis remarkably in NAFLD mice. The determination of biochemical indicators showed that SCO could inhibit the increased serum transaminase activity and liver lipid level induced by HFD. RNA sequencing analysis of liver tissues found that 2742 and 3663 genes were significantly changed by HFD and SCO, respectively. SCO reversed the most of genes involved in cholesterol synthesis and fatty acid (triglyceride) metabolism induced by HFD. the results of the validation experiment were mostly consistent with the RNA sequencing. SCO alleviated liver injury and steatosis in NAFLD mice, which may be closely related to the regulation of cholesterol and fatty acid (triglyceride) metabolism.
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