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反式查尔酮对单纯性脂肪变性向非酒精性脂肪性肝炎进展的保护作用:miR-122、21、34a和451的调控

Protective Role of trans-Chalcone against the Progression from Simple Steatosis to Non-alcoholic Steatohepatitis: Regulation of miR-122, 21, 34a, and 451.

作者信息

Karimi-Sales Elham, Jeddi Sajad, Ebrahimi-Kalan Abbas, Alipour Mohammad Reza

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Adv Pharm Bull. 2022 Jan;12(1):200-205. doi: 10.34172/apb.2022.022. Epub 2021 Jan 31.

Abstract

Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder and an aggressive form of fatty liver disease. Certain microRNAs, including miR-122, 21, 34a, and 451, are involved in the transition from steatosis to NASH. This study examined how trans-chalcone (the core of chalcone derivatives) affects NAFLD progression by regulating miRNAs. Male rats were divided into three groups (n = 7/group) as follows: control, rats were gavaged with 10% tween 80 (for two weeks); NASH, rats were gavaged with a high-fat liquid diet (HFD; for six weeks) and 10% tween 80 (for two weeks); NASH + Chal, rats were gavaged with the HFD (for six weeks) and trans-chalcone (for two weeks). Hepatic expression levels of miR-122, 21, 34a, and 451 were determined. trans-Chalcone reversed histological abnormalities, reduced liver injury markers, and attenuated insulin resistance in HFD-fed rats. In the liver, HFD-induced NASH increased the expression level of miR-34a and decreased expression levels of miR-122, 21, and 451. However, trans-chalcone inhibited HFD-induced changes in expression levels of these miRNAs. trans-Chalcone could inhibit the transition from steatosis to NASH through the modulation of miR-122, 21, 34a, and 451 expression levels in the liver.

摘要

非酒精性脂肪性肝炎(NASH)是一种炎症性疾病,也是一种侵袭性形式的脂肪肝疾病。某些微小RNA,包括miR-122、21、34a和451,参与了从脂肪变性到NASH的转变过程。本研究探讨了反式查尔酮(查尔酮衍生物的核心)如何通过调节微小RNA来影响非酒精性脂肪性肝病(NAFLD)的进展。雄性大鼠被分为三组(每组n = 7),如下所示:对照组,大鼠灌胃10%吐温80(持续两周);NASH组,大鼠灌胃高脂液体饮食(HFD;持续六周)和10%吐温80(持续两周);NASH + Chal组,大鼠灌胃HFD(持续六周)和反式查尔酮(持续两周)。测定肝脏中miR-122、21、34a和451的表达水平。反式查尔酮可逆转HFD喂养大鼠的组织学异常,降低肝脏损伤标志物,并减轻胰岛素抵抗。在肝脏中,HFD诱导的NASH增加了miR-34a的表达水平,并降低了miR-122、21和451的表达水平。然而,反式查尔酮抑制了HFD诱导的这些微小RNA表达水平的变化。反式查尔酮可通过调节肝脏中miR-122、21、34a和451的表达水平来抑制从脂肪变性到NASH的转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db7b/9012929/bc36ea48afa2/apb-12-200-g001.jpg

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