Department of Biochemistry, School of Medicine Iran University of Medical Sciences, Tehran, Iran.
Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
DNA Cell Biol. 2023 Feb;42(2):82-90. doi: 10.1089/dna.2022.0581. Epub 2023 Feb 1.
The present study was designed to evaluate the effects of resveratrol, atorvastatin, and a combination of resveratrol and atorvastatin on expression levels of genes involved in the cholesterol metabolic pathway in the fatty liver of C57/BL6 mice. A high-fat diet was used to induce fatty liver in C57/BL6 mice treated with resveratrol, atorvastatin, or a combination of resveratrol and atorvastatin. Pathological and biochemical studies were performed. In addition, hepatic gene expressions of ATP-binding cassette transporter A1 (), , liver X receptor ()α, scavenger receptor B1 (), low-density lipoprotein receptor (), and miR33 were evaluated by the real-time PCR method, and the Western blot method was used to measure the ABCA1, ABCG1, and LXRα protein levels. Resveratrol and atorvastatin reduced fat accumulation in the liver of mice with fatty liver, and this effect was correlated with decreased blood glucose levels, triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol blood levels compared with the positive control (PC) group. In contrast to the animals of the PC group, fatty liver groups that received resveratrol and atorvastatin had a significant effect on the mRNA levels of the , , α, , , and miR33 genes. Moreover, resveratrol and atorvastatin administration elevated ABCA1 and ABCG1 and reduced LXRα protein expression. Obtained results showed that resveratrol and atorvastatin combination therapy can improve nonalcoholic fatty liver disease by targeting genes involved in cholesterol metabolism and miR33.
本研究旨在评估白藜芦醇、阿托伐他汀和白藜芦醇与阿托伐他汀联合应用对 C57/BL6 小鼠脂肪肝胆固醇代谢途径相关基因表达水平的影响。采用高脂饮食诱导 C57/BL6 小鼠脂肪肝，并用白藜芦醇、阿托伐他汀或白藜芦醇与阿托伐他汀联合处理。进行了病理和生化研究。此外，采用实时 PCR 法检测肝组织中 ATP 结合盒转运体 A1 ()、 、肝 X 受体 ()α、清道夫受体 B1 (), 、低密度脂蛋白受体 ()和 miR33 的基因表达，采用 Western blot 法检测 ABCA1、ABCG1 和 LXRα 蛋白水平。白藜芦醇和阿托伐他汀可减少脂肪肝小鼠肝脏脂肪堆积，这种作用与降低血糖水平、甘油三酯、胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平相关，与阳性对照组（PC）相比。与 PC 组动物相比，接受白藜芦醇和阿托伐他汀治疗的脂肪肝组，,, α,,, 和 miR33 基因的 mRNA 水平有显著影响。此外，白藜芦醇和阿托伐他汀给药可提高 ABCA1 和 ABCG1 并降低 LXRα 蛋白表达。研究结果表明，白藜芦醇和阿托伐他汀联合治疗可通过靶向胆固醇代谢相关基因和 miR33 改善非酒精性脂肪性肝病。
