Polydatin alleviated alcoholic liver injury in zebrafish larvae through ameliorating lipid metabolism and oxidative stress
Polydatin alleviated alcoholic liver injury in zebrafish larvae through ameliorating lipid metabolism and oxidative stress
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虎杖甙通过改善脂质代谢和氧化应激减轻斑马鱼幼虫酒精性肝损伤
DOI：
10.1016/j.jphs.2018.08.007
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Lv, Zhiping
中科院分区：
文献类型：
--
作者：
Lai, Yuling;Zhou, Chuying;Lv, Zhiping
肝脂肪变性是酒精性肝病（ALD）的早期阶段，可进展为脂肪性肝炎、纤维化甚至肝硬化。虎杖苷是虎杖的主要活性成分。et Zucc，已被认为具有保肝和抗炎特性。为探讨虎杖苷是否能抑制乙醇诱导的肝损伤并阐明其分子机制，将受精后4 d的斑马鱼幼鱼暴露于350 mmol/L乙醇中32 h，然后用虎杖苷处理48 h。油红O、尼罗红、H&E染色观察肝脏病理变化。采用定量PCR方法检测mRNA水平，H2 O2特异性荧光探针检测抗氧化能力。在这里，虎杖苷强烈减轻肝脂肪变性，并降低酒精和脂质代谢相关基因的表达水平，包括CYP 2 Y3，CYP 3A 65，HMGCRa，HMGCRb和FcR。此外，虎杖苷抑制肝脏氧化应激根据荧光探针。此外，DNA损伤相关基因（CHOP，GADD 45 α a）的表达显着上调表明，虎杖苷减弱了幼虫的肝细胞凋亡。因此，虎杖苷可能通过减轻肝脏脂肪堆积，改善脂质和乙醇代谢，减轻氧化应激和DNA损伤，从而改善急性酒精性肝损伤斑马鱼的肝功能。(C)2018作者Elsevier B. V.代表日本药理学会制作和主办。
Hepatic steatosis is the early stage of alcoholic liver disease (ALD), may progress to steatohepatitis, fibrosis even cirrhosis. Polydatin, the primary active component of Polygonum cuspidatum Sieb. et Zucc, has been recognized to possess hepatoprotective and anti-inflammatory properties. To investigate whether polydatin alleviates ethanol induced liver injury and to elucidate the underlying molecular mechanisms, zebrafish larvae at 4 days post-fertilization (dpf) were exposed to 350 mmol/L of ethanol for 32 h, then treated with polydatin for 48 h. Oil red O, Nile Red and H&E staining were used to analyze the pathological changes in liver. The mRNA levels were measured by quantitative PCR and the antioxidant capacity was detected using H2O2-specific fluorescent probe. Here, polydatin strongly alleviated hepatic steatosis and decreased the expression levels of alcohol and lipid metabolism-related genes, including CYP2Y3, CYP3A65, HMGCRa, HMGCRb and FASN. Additionally, polydatin inhibited oxidative stress in the liver according to fluorescent probe. Moreover, significantly up-regulated expression of DNA damage-related genes (CHOP, GADD45 alpha a) revealed that polydatin attenuated hepatic apoptosis in larvae. In conclusion, polydatin may improve the liver function of zebrafish with acute alcoholic liver injury through attenuating hepatic fat accumulation, ameliorating lipid and ethanol metabolism and reducing oxidative stress and DNA damage. (C) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.