Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae.
Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae.
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橙皮苷通过改善斑马鱼幼虫的脂质代谢和细胞损伤来防止急性酒精损伤。
DOI：
10.1155/2017/7282653
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lv Z
中科院分区：
文献类型：
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作者：
Zhou Z;Zhong W;Lin H;Huang P;Ma N;Zhang Y;Zhou C;Lai Y;Huang S;Huang S;Gao L;Lv Z
酒精性肝病（ALD）是一系列肝功能异常，包括酒精性脂肪变性、脂肪性肝炎和肝硬化。橙皮苷是葡萄柚黄酮的主要成分，多种动物实验证明橙皮苷具有抗氧化、抗炎、减轻多器官损伤的作用。然而，酒精性肝损伤抵抗的潜在机制尚不清楚。因此，本研究旨在探讨橙皮苷对ALD的保护作用及其分子机制。以野生型和转基因的肝脏特异性eGFP表达Tg （lfabp10α:eGFP）斑马鱼幼鱼（4 dpf）为材料，建立了350 mM乙醇诱导32 h的ALD斑马鱼幼鱼模型。结果显示，与ALD模型相比，橙皮苷可显著降低肝脏形态学损伤及酒精和脂质代谢相关基因cyp2y3、cyp3a65、hmgcra、hmgcrb、fasn、fads2的表达。此外，研究结果表明橙皮苷还能减轻肝损伤，这体现在内质网应激和DNA损伤相关基因（chop、gadd45αa和edem1）的表达上。综上所述，橙皮苷可通过减轻内质网应激和DNA损伤，调节酒精和脂质代谢，抑制酒精对斑马鱼幼鱼肝脏的损伤。
Alcoholic liver disease (ALD) is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP) zebrafish larvae (4 dpf). The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1). In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism.