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Nonalcoholic Steatohepatitis

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关键词消化 疾病 炎症

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解析

nonalcoholic 英 [,nɒnælkə'hɒlɪk] 美 [,nɑn,ælkə'hɑlɪk]

释义   adj. 不含酒精的

例句   Insulin resistance, diabetes and high levels of cholesterol all contribute to the development of nonalcoholic fatty liver disease and its complications. 胰岛素抵抗、糖尿病及高水平的胆固醇均导致非酒精性脂肪肝的发展及并发症的产生。

 

steatohepatitis 英 [,stiə'to ˌhepəˈtaɪtɪs] 美 [,stiə'to ˌhɛpəˈtaɪtɪs]

释义   n. 脂肪性肝炎

例句   To explore the risk factors of non-alcoholic steatohepatitis(NASH) in children. 探讨儿童非酒精性脂肪性肝炎(NASH)的危险因素。


概述

非酒精性脂肪性肝炎(nonalcoholic steatohepatitis ,NASH)又称代谢性脂肪性肝炎,是一种以脂肪在肝脏中过量蓄积为主要特征的慢性肝病,与酒精性肝病类似,但发生在不喝酒或者少喝酒的人身上,日常生活中摄入过量脂肪也可能发病,并有较高风险发展成肝硬化和肝癌。非酒精性脂肪性肝炎与肥胖、胰岛素抵抗、Ⅱ型糖尿病、高脂血症等代谢紊乱关系密切,其主要特征为肝细胞损伤、肝脏炎症、进行性纤维化,已经成为了肝衰竭和肝细胞癌的最重要原因。 病因和发病机制NA

Carbon monoxide releasing molecule-A1 improves nonalcoholic steatohepatitis via Nrf2 activation mediated improvement in oxidative stress and mitochondrial function复制标题

一氧化碳释放molecule-A1通过Nrf2激活介导的氧化应激和线粒体功能改善非酒精性脂肪性肝炎

发表时间:2019-08-31

影响因子:7.8

作者: Kapil K. Upadhyay

期刊:Redox Biology

Nuclear factor-erythroid 2 related factor 2 (Nrf2)-mediated signaling plays a central role in maintaining cellular redox homeostasis of hepatic cells. Carbon monoxide releasing molecule-A1 (CORM-A1) has been reported to stimulate up-regulation and nuclear translocation of Nrf2 in hepatocytes. However, the role of CORM-A1 in improving lipid metabolism, antioxidant signaling and mitochondrial functions in nonalcoholic steatohepatitis (NASH) is unknown. In this study, we report that CORM-A1 prevents hepatic steatosis in high fat high fructose (HFHF) diet fed C57BL/6J mice, used as model of NASH. The beneficial effects of CORM-A1 in HFHF fed mice was associated with improved lipid homeostasis, Nrf2 activation, upregulation of antioxidant responsive (ARE) genes and increased ATP production. As, mitochondria are intracellular source of reactive oxygen species (ROS) and important sites of lipid metabolism, we further investigated the mechanisms of action of CORM-A1-mediated improvement in mitochondrial function in palmitic acid (PA) treated HepG2 cells. Cellular oxidative stress and cell viability were found to be improved in PA + CORM-A1 treated cells via Nrf2 translocation and activation of cytoprotective genes. Furthermore, in PA treated cells, CORM-A1 improved mitochondrial oxidative stress, membrane potential and rescued mitochondrial biogenesis thru upregulation of Drp1, TFAM, PGC-1α and NRF-1 genes. CORM-A1 treatment improved cellular status by lowering glycolytic respiration and maximizing OCR. Improvement in mitochondrial respiration and increment in ATP production in PA + CORM-A1 treated cells further corroborate our findings. In summary, our data demonstrate for the first time that CORM-A1 ameliorates tissue damage in steatotic liver via Nrf2 activation and improved mitochondrial function, thus, suggesting the anti-NASH potential of CORM-A1.

译文

核因子 - 红细胞2相关因子2(Nrf2)介导的信号传导在维持肝细胞的细胞氧化还原稳态中起重要作用。据报道,一氧化碳释放分子-A1(CORM-A1)刺激肝细胞中Nrf2的上调和核转位。然而,CORM-A1在改善非酒精性脂肪性肝炎(NASH)中脂质代谢,抗氧化信号和线粒体功能方面的作用尚不清楚。在这项研究中,我们报道CORM-A1预防高脂高果糖(HFHF)饮食喂养的C57BL / 6J小鼠的肝脂肪变性,用作NASH的模型。 CORM-A1在HFHF喂养的小鼠中的有益作用与改善的脂质稳态,Nrf2活化,抗氧化应答(ARE)基因的上调和ATP产生增加有关。由于线粒体是活性氧(ROS)的细胞内来源和脂质代谢的重要部位,我们进一步研究了CORM-A1介导的改善棕榈酸(PA)处理的HepG2细胞中线粒体功能的作用机制。通过Nrf2易位和细胞保护基因的激活,发现PA + CORM-A1处理的细胞中的细胞氧化应激和细胞活力得到改善。此外,在PA处理的细胞中,CORM-A1通过上调Drp1,TFAM,PGC-1α和NRF-1基因改善了线粒体氧化应激,膜电位和拯救的线粒体生物合成。 CORM-A1治疗通过降低糖酵解呼吸和最大化OCR来改善细胞状态。 PA + CORM-A1处理细胞中线粒体呼吸的改善和ATP产生的增加进一步证实了我们的研究结果。总之,我们的数据首次证明CORM-A1通过Nrf2激活和改善线粒体功能改善脂肪肝组织损伤,因此,提示CORM-A1的抗NASH潜力。