Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran; Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran.
Department of Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Biomed Pharmacother. 2018 Sep;105:144-150. doi: 10.1016/j.biopha.2018.05.121. Epub 2018 May 28.
The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent.
慢性酒精消费与酒精性肝病的发展之间的关联是一个非常熟知的现象，但涉及乙醇诱导的肝损伤的确切潜在分子介质仍难以捉摸。本研究旨在描述在单独或联合生姜提取物的大量乙醇暴露下肝脏中脂质代谢改变以及与脂质代谢相关的分子介质。将 24 只雄性 wistar 大鼠分为三组，即对照组、乙醇组和生姜提取物处理的乙醇组（GETE 组）。治疗 6 周后，与对照组相比，乙醇组脂肪酸易位酶（FAT）/CD36、蛋白酪氨酸磷酸酶 1B（PTP1B）基因表达显著增加，肝细胞核因子 4α（HNF4A）基因表达显著降低。与对照组相比，乙醇给药还显著增加了血浆 LDL、胆固醇、甘油三酯、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。此外，与对照组相比，乙醇组显示出肝脏组织学变化，如纤维化、局灶性微泡性脂肪变性、一些凋亡的肝细胞、斑片状坏死、门脉淋巴细胞炎症、Mallory-Denk 小体、巨大线粒体、碎片状坏死。与乙醇组相比，生姜提取物与乙醇一起消耗，部分改善了基因表达改变和组织学变化，改善了不理想的脂质谱和肝脏酶变化。这些发现表明，乙醇诱导的肝脏异常可能部分与 FAT/CD36、PTP1B 过表达和 HNF4A 基因下调介导的脂质动态平衡变化有关。它还表明，这些影响可以通过使用生姜提取物作为抗氧化剂和抗炎剂来减轻。
