Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down-regulating BRD4
Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down-regulating BRD4
复制标题
丹酚酸 A 通过下调 BRD4 抑制 HMGB1 易位，缓解慢性酒精性肝病
DOI：
10.1111/jcmm.15473
复制
发表时间：
2020-06-29
影响因子：
5.3
通讯作者：
Yao, Jihong
中科院分区：
文献类型：
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作者：
Lan, Yanwen;Yan, Ran;Yao, Jihong
酒精性肝病（ALD）是慢性肝病的主要原因，也是全球健康问题。ALD的发病机制始于肝脏脂肪变性，并且ALD可以进展为脂肪性肝炎、纤维化、肝硬化甚至肝细胞癌。丹参素A（SalvianicAcidA，SAA）是丹参中的一种酚酸类成分，具有保肝作用。本研究旨在探讨SAA对慢性酒精性肝损伤的作用及其分子机制。我们发现，SAA显着抑制酒精诱导的肝损伤和改善乙醇诱导的肝脏炎症。SAA的这些保护作用可能是通过抑制BRD 4/HMGB 1信号通路来实现的，因为SAA处理在很大程度上减少了酒精诱导的BRD 4表达和HMGB 1核转位和释放。重要的是，BRD 4敲低阻止了AML-12细胞中乙醇诱导的HMGB 1释放和炎性细胞因子的产生。类似地，酒精诱导的促炎细胞因子被HMGB 1 siRNA阻断。总的来说，我们的研究结果表明，BRD 4/HMGB 1通路的激活参与了ALD的发病机制。因此，通过SAA治疗等策略操纵BRD 4/HMGB 1通路对慢性酒精性肝病治疗具有巨大的治疗潜力。
Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol-induced liver injury and ameliorated ethanol-induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol-induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol-induced HMGB1 release and inflammatory cytokine production in AML-12 cells. Similarly, alcohol-induced pro-inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.