Naringin attenuates alcoholic liver injury by reducing lipid accumulation and oxidative stress
Naringin attenuates alcoholic liver injury by reducing lipid accumulation and oxidative stress
复制标题
柚皮苷通过减少脂质积累和氧化应激来减轻酒精性肝损伤
DOI：
10.1016/j.lfs.2018.07.031
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发表时间：
2019-01-01
期刊：
影响因子：
6.1
通讯作者：
Gao, Lei
中科院分区：
文献类型：
--
作者：
Zhou, Chuying;Lai, Yuling;Gao, Lei
目的：酒精性肝病(ALD)是世界范围内最大的健康风险之一，可导致肝脏脂肪变性、进行性纤维化、肝硬变甚至癌症。柚皮苷是葡萄柚中含量丰富的黄烷酮类化合物，具有抗氧化应激和抗炎作用，对多器官损伤具有保护作用，是治疗酒精性肝病的潜在药物。然而，防止酒精损伤的具体机制仍不完全清楚。本研究旨在探讨酒精暴露对斑马鱼幼体系统肝脏和全身的影响及其调节机制。主要方法：将野生型斑马鱼幼体(WT)和肝脏特异表达的转基因斑马鱼(Tg(lFabp10α：EGFP))受精后96h暴露于2%乙醇中32h，建立ALD模型。选择不同的终点，如肝脏形态和大小的变化，组织学变化，氧化应激相关自由基水平，细胞凋亡和某些基因的表达，验证了柚皮苷在酒精性肝损伤中的本质影响。关键发现：随后的实验，包括油红O，尼罗红，病理苏木素和伊红(H&E)，TUNEL染色和定量聚合酶链式反应显示，柚皮苷治疗减轻酒精性肝脂肪变性，这种抑制作用呈剂量依赖关系。具体来说，25 mg/L剂量的反应几乎正常。意义：这一发现表明，柚皮苷可能通过减少脂质堆积，减少氧化应激和细胞凋亡，抑制酒精诱导的肝脏脂肪变性和损伤。
Aims: Alcoholic liver disease (ALD) is a leading health risk worldwide, which can induce hepatic steatosis, progressive fibrosis, cirrhosis and even carcinoma. As a potential therapeutic drug for ALD, naringin, an abundant flavanone in grapefruit, could improve resistance to oxidative stress and inflammation and protects against multiple organ injury. However, the specific mechanisms responsible for protection against alcoholic injury remain not fully understood. In this study, we aim to investigate the effect and the regulatory mechanisms of naringin in the liver and whole body after alcohol exposure under zebrafish larvae system.Main methods: At 96 h post fertilization (hpf), larvae from wild-type (WT) and transgenic zebrafish, with liver-specific eGFP expression (Tg(lfabp10 alpha: eGFP)), were exposed to 2% ethanol for 32 h to establish an ALD model. Different endpoints, such as morphological changes in liver shape and size, histological changes, oxidative stress-related free radical levels, apoptosis and the expression of certain genes, were chosen to verify the essential impact of naringin in alcohol-induced liver lesions.Key findings: Subsequent experiments, including Oil red O, Nile red, pathological hematoxylin and eosin (H&E), and TUNEL staining and qPCR, revealed that naringin treatment reduced alcoholic hepatic steatosis, and this inhibitory effect was dose dependent. Specifically, a 25 mg/L dose resulted in an almost normal response.Significance: This finding suggested that naringin may inhibit alcoholic-induced liver steatosis and injury by attenuating lipid accumulation and reducing oxidative stress and apoptosis.