Lee Ran, Lee Won-Yong, Park Hyun-Jung
Department of Livestock, Korea National University of Agriculture and Fisheries, Jeonju 54874, Republic of Korea.
Department of Animal Biotechnology, College of Life Science, Sangji University, Wonju-si 26339, Republic of Korea.
Curr Issues Mol Biol. 2023 Oct 17;45(10):8412-8426. doi: 10.3390/cimb45100530.
Melatonin, a hormone secreted by the pineal gland of vertebrates, regulates sleep, blood pressure, and circadian and seasonal rhythms, and acts as an antioxidant and anti-inflammatory agent. We investigated the protective effects of melatonin against markers of D-galactose (D-Gal)-induced hepatocellular aging, including liver inflammation, hepatocyte structural damage, and non-alcoholic fatty liver. Mice were divided into four groups: phosphate-buffered saline (PBS, control), D-Gal (200 mg/kg/day), melatonin (20 mg/kg), and D-Gal (200 mg/kg) and melatonin (20 mg) cotreatment. The treatments were administered once daily for eight consecutive weeks. Melatonin treatment alleviated D-Gal-induced hepatocyte impairment. The AST level was significantly increased in the D-Gal-treated groups compared to that in the control group, while the ALT level was decreased compared to the melatonin and D-Gal cotreated group. Inflammatory genes, such as IL1-β, NF-κB, IL-6, TNFα, and iNOS, were significantly increased in the D-Gal aging model, whereas the expression levels of these genes were low in the D-Gal and melatonin cotreated group. Interestingly, the expression levels of hepatic steatosis-related genes, such as LXRα, C/EBPα, PPARα, ACC, ACOX1, and CPT-1, were markedly decreased in the D-Gal and melatonin cotreated group. These results suggest that melatonin suppresses hepatic steatosis and inflammation in a mouse model of D-Gal-induced aging.
褪黑素是脊椎动物松果体分泌的一种激素，可调节睡眠、血压以及昼夜节律和季节性节律，并具有抗氧化和抗炎作用。我们研究了褪黑素对D-半乳糖（D-Gal）诱导的肝细胞衰老标志物的保护作用，包括肝脏炎症、肝细胞结构损伤和非酒精性脂肪肝。将小鼠分为四组：磷酸盐缓冲盐水（PBS，对照组）、D-Gal（200 mg/kg/天）、褪黑素（20 mg/kg）以及D-Gal（200 mg/kg）与褪黑素（20 mg）联合治疗组。连续八周每天给药一次。褪黑素治疗减轻了D-Gal诱导的肝细胞损伤。与对照组相比，D-Gal治疗组的AST水平显著升高，而与D-Gal和褪黑素联合治疗组相比，ALT水平降低。在D-Gal衰老模型中，炎症基因如IL1-β、NF-κB、IL-6、TNFα和iNOS显著增加，而在D-Gal和褪黑素联合治疗组中这些基因的表达水平较低。有趣的是，在D-Gal和褪黑素联合治疗组中，肝脂肪变性相关基因如LXRα、C/EBPα、PPARα、ACC、ACOX1和CPT-1的表达水平明显降低。这些结果表明，在D-Gal诱导衰老的小鼠模型中，褪黑素可抑制肝脏脂肪变性和炎症。
