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低聚原花青素对小鼠酒精性肝脂肪变性和损伤的保护作用。

Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice.

作者信息

Wang Zhiguo, Su Bo, Fan Sumei, Fei Haixia, Zhao Wei

机构信息

Hospital of Integrated Chinese and Western Medicine in Jiangsu Province, Jiangsu, China.

Huai'an Maternity and Child Health-Care Hospital, Huai'an, China.

出版信息

Biochem Biophys Res Commun. 2015 Mar 20;458(4):757-62. doi: 10.1016/j.bbrc.2015.01.153. Epub 2015 Feb 11.

Abstract

The long-term consumption of alcohol has been associated with multiple pathologies at all levels, such as alcoholism, chronic pancreatitis, malnutrition, alcoholic liver disease (ALD) and cancer. In the current study, we investigated the protective effect of oligomeric proanthocyanidins (OPC) against alcohol-induced liver steatosis and injury and the possible mechanisms using ethanol-induced chronic liver damage mouse models. The results showed that OPC significantly improved alcohol-induced dyslipidemia and alleviated liver steatosis by reducing levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-c) and liver malondialdehyde (MDA), and increasing levels of serum high-density lipoprotein (HDL-c), liver superoxide dismutase (SOD). Further investigation indicated that OPC markedly decreased the expressions of lipid synthesis genes and inflammation genes such as sterol regulatory element-binding protein-1c (Srebp-1c), protein-2 (Srebp2), interleukin IL-1β, IL-6 and TNF-α. Furthermore, AML-12 cells line was used to investigate the possible mechanisms which indicated that OPC might alleviate liver steatosis and damage through AMP-activated protein kinase (AMPK) activation involving oxidative stress. In conclusion, our study demonstrated excellent protective effect of OPC against alcohol-induced liver steatosis and injury, which could a potential drug for the treatment of alcohol-induced liver injury in the future.

摘要

长期饮酒与各个层面的多种病症相关,如酒精中毒、慢性胰腺炎、营养不良、酒精性肝病(ALD)和癌症。在本研究中,我们使用乙醇诱导的慢性肝损伤小鼠模型,研究了低聚原花青素(OPC)对酒精诱导的肝脂肪变性和损伤的保护作用及其可能的机制。结果表明,OPC通过降低血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总甘油三酯(TG)、总胆固醇(TC)、低密度胆固醇(LDL-c)和肝脏丙二醛(MDA)水平,并提高血清高密度脂蛋白(HDL-c)、肝脏超氧化物歧化酶(SOD)水平,显著改善了酒精诱导的血脂异常并减轻了肝脂肪变性。进一步研究表明,OPC显著降低了脂质合成基因和炎症基因如固醇调节元件结合蛋白-1c(Srebp-1c)、蛋白-2(Srebp2)、白细胞介素IL-1β、IL-6和肿瘤坏死因子-α的表达。此外,使用AML-12细胞系研究可能的机制,结果表明OPC可能通过涉及氧化应激的AMP活化蛋白激酶(AMPK)激活来减轻肝脂肪变性和损伤。总之,我们的研究证明了OPC对酒精诱导的肝脂肪变性和损伤具有出色的保护作用,这可能成为未来治疗酒精性肝损伤的一种潜在药物。

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