Naringenin inhibits alcoholic injury by improving lipid metabolism and reducing apoptosis in zebrafish larvae
Naringenin inhibits alcoholic injury by improving lipid metabolism and reducing apoptosis in zebrafish larvae
复制标题
柚皮素通过改善斑马鱼幼虫的脂质代谢和减少细胞凋亡来抑制酒精损伤。
DOI：
10.3892/or.2017.5965
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发表时间：
2017-11-01
期刊：
影响因子：
4.2
通讯作者：
Lv, Zhiping
中科院分区：
文献类型：
--
作者：
Lin, Haiyan;Zhou, Zhenting;Lv, Zhiping
酒精性肝病 (ALD) 包括一系列肝脏异常，从孤立性酒精性脂肪变性到脂肪性肝炎和肝硬化。柚皮素是葡萄柚中的主要黄烷酮，可增强对氧化应激和炎症的抵抗力，并防止各种动物模型中的多器官损伤。然而，人们对防止酒精损伤的具体机制知之甚少。在本研究中，我们旨在研究柚皮素对酒精事件的影响以及斑马鱼幼虫暴露于350 mmol/l乙醇32小时后肝脏和全身中柚皮素的分子调节机制。斑马鱼幼虫 {受精后 4 天 (dpf)；采用野生型(WT)和肝脏特异性eGFP表达的转基因株系[Tg(lfabp10α-eGFP)]}建立酒精性脂肪肝模型，以评价柚皮素治疗抗酒精损伤的效果。柚皮素显着降低斑马鱼幼虫的酒精肝形态表型以及酒精和脂质代谢相关基因的表达，包括 cyp2y3、cyp3a65、hmgcra、hmgcrb、fasn、fabp10α、fads2 和 echs1。通过 TUNEL 染色检测发现，柚皮素还可以减弱幼虫的肝细胞凋亡，这与内质网应激关键生物标志物和 DNA 损伤基因（chop、gadd45αa 和 edem1）的表达一致。本研究表明柚皮素通过减少细胞凋亡和 DNA 损伤以及协调酒精和脂质代谢来抑制酒精诱导的斑马鱼幼虫肝脏脂肪变性和损伤。
Alcoholic liver disease (ALD) includes a spectrum of hepatic abnormalities that range from isolated alcoholic steatosis to steatohepatitis and cirrhosis. Naringenin, a predominant flavanone in grapefruit, increases resistance to oxidative stress and inflammation and protects against multiple organ injury in various animal models. However, the specific mechanisms responsible for protection against alcoholic injury are poorly understood. In the present study, we aimed to investigate the effect of naringenin on alcoholic events and the molecular regulatory mechanisms of naringenin in the liver and whole body of zebrafish larvae following exposure to 350 mmol/l ethanol for 32 h. Zebrafish larvae {4 days post‑fertilization (dpf); wild-type (WT) and a transgenic line with liver-specific eGFP expression [Tg(lfabp10α-eGFP)]} were used to establish an alcoholic fatty liver model in order to evaluate the effects of naringenin treatment on anti-alcoholic injury. Naringenin significantly reduced alcoholic liver morphological phenotypes and the expression of alcohol and lipid metabolism-related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, fabp10α, fads2 and echs1, in zebrafish larvae. Naringenin also attenuated hepatic apoptosis in larvae as detected by TUNEL staining, consistent with the expression of critical biomarkers of endoplasmic reticulum stress and of DNA damage genes (chop, gadd45αa and edem1). The present study showed that naringenin inhibited alcohol-induced liver steatosis and injury in zebrafish larvae by reducing apoptosis and DNA damage and by harmonizing alcohol and lipid metabolism.