P-Hydroxyacetophenone Ameliorates Alcohol-Induced Steatosis and Oxidative Stress via the NF-κB Signaling Pathway in Zebrafish and Hepatocytes
P-Hydroxyacetophenone Ameliorates Alcohol-Induced Steatosis and Oxidative Stress via the NF-κB Signaling Pathway in Zebrafish and Hepatocytes
复制标题
P-羟基苯乙酮通过 NF-κB 信号通路改善斑马鱼和肝细胞中酒精引起的脂肪变性和氧化应激。
DOI：
10.3389/fphar.2019.01594
复制
发表时间：
2020-01-28
影响因子：
5.6
通讯作者：
Gao, Lei
中科院分区：
文献类型：
--
作者：
Huang, Sha;Zhou, Chuying;Gao, Lei
酒精性肝病（alcoholic liver disease，ALD）是一种严重的全球性健康问题，它是酒精性肝病的直接后果，可导致酒精性脂肪肝、酒精性脂肪性肝炎、肝纤维化和肝硬化。对羟基苯乙酮（p-HAP）主要用作利胆保肝化合物，具有抗B型肝炎、抗氧化和抗炎作用。然而，目前还没有关于p-HAP在ALD中的实验报道，p-HAP在ALD中的作用和机制尚不清楚。此外，目前尚无关于p-HAP治疗ALD的研究。p-HAP抗急性酒精性肝损伤的分子机制尚不清楚。在这项研究中，我们的目的是调查是否p-HAP消除ALD，并阐明潜在的分子机制。在受精后第4天（dpf），用350 mmol/l乙醇浸泡斑马鱼幼鱼32 h，然后用p-HAP处理48 h。我们选择了各种结果指标，如肝组织形态学变化，抗氧化和抗凋亡能力以及炎症相关蛋白的表达，以阐明p-HAP治疗酒精性肝损伤的根本机制。采用HE染色、尼罗红染色和油红O染色观察肝组织形态学和脂质的变化。我们还使用TUNEL染色，免疫组化和Western印迹分析，以揭示凋亡和炎症相关蛋白的变化。特别地，我们使用多种荧光探针检测p-HAP在活体斑马鱼幼体中的抗氧化能力。此外，我们发现p-HAP治疗以剂量依赖性方式缓解酒精性肝脂肪变性，并且50 μ M剂量具有最佳治疗效果。总之，本研究表明p-HAP可能通过NF-κ B B信号通路在体内外降低氧化应激和细胞凋亡。
Alcoholic liver disease (ALD), which is recognized as an important health problem worldwide, is a direct consequence of alcohol consumption, which can induce alcoholic fatty liver, alcoholic steatohepatitis, fibrosis and cirrhosis. P-Hydroxyacetophenone (p-HAP) is mainly used as a choleretic and hepatoprotective compound and has anti-hepatitis B, antioxidative and anti-inflammatory effects. However, no experimental report has focused on p-HAP in ALD, and the effect and mechanism of p-HAP in ALD remain unknown. In addition, there is no research on p-HAP in the treatment of ALD. The potential molecular mechanisms of p-HAP against acute alcoholic liver injury remain unknown. In this study, we aimed to investigate whether p-HAP alleviates ALD and to clarify the potential molecular mechanisms. Zebrafish larvae were soaked in 350 mmol/l ethanol for 32 h at 4 days post fertilization (dpf) and then treated with p-HAP for 48 h. We chose various outcome measures, such as liver histomorphological changes, antioxidation and antiapoptosis capability and expression of inflammation-related proteins, to elucidate the essential mechanism of p-HAP in the treatment of alcohol-induced liver damage. Subsequently, we applied pathological hematoxylin and eosin (H&E) staining, Nile red staining and oil red O staining to detect the histomorphological and lipid changes in liver tissues. We also used TUNEL staining, immunochemistry and Western blot analysis to reveal the changes in apoptosis- and inflammation-related proteins. In particular, we used a variety of fluorescent probes to detect the antioxidant capacity of p-HAP in live zebrafish larvae in vivo. In addition, we discovered that p-HAP treatment relieved alcoholic hepatic steatosis in a dose-dependent manner and that the 50 mu M dose had the best therapeutic effect. Generally, this research indicated that p-HAP might reduce oxidative stress and cell apoptosis in vivo and in vitro via the NF-kappa B signaling pathway.