Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Medical Science Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Lipids Health Dis. 2020 May 8;19(1):88. doi: 10.1186/s12944-020-01276-w.
Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear.
In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%.
The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P < 0.05). Moreover, CS exposure decreased the LDLR expression in the hepatocytes and promoted inflammation in the blood vessel walls. Melatonin was intraperitoneally injected at 10 mg/kg/d for 6 weeks alongside CS exposure, and this significantly decreased the levels of TC, TGs, and LDL-C and decreased the expression of intercellular adhesion molecule-1 and the infiltration of cluster determinant 68-cells. In vitro, CS extract prepared by bubbling CS through phosphate-buffered saline decreased the LDLR expression in HepG2 cells in a time- and concentration-dependent manner, and this effect was prevented by pretreatment with 100 μM melatonin.
In conclusion, CS exposure impaired lipid metabolism and decreased LDLR expression in hepatocytes, and these effects could be prevented by melatonin supplementation. These findings implied that melatonin has the potential therapeutic applicability in the prevention of lipid metabolic disorder in smokers.
香烟烟雾（CS）暴露会损害血清脂质谱和血管内皮细胞的功能，从而加速动脉粥样硬化。然而，CS 暴露对肝脏中低密度脂蛋白受体（LDLR）表达的确切机制和影响仍不清楚。
在这项研究中，成年雄性 C57BL/6J 小鼠被分为三组，一组暴露于 CS 中 6 周。用 CS 提取物以 1、2.5、5 和 10%的浓度处理 HepG2 细胞。
CS 暴露组的血清总胆固醇（TC）、甘油三酯（TGs）和低密度脂蛋白胆固醇（LDL-C）水平明显高于对照组（P<0.05）。此外，CS 暴露降低了肝细胞中的 LDLR 表达，并促进了血管壁的炎症。CS 暴露的同时，腹腔内注射 10mg/kg/d 的褪黑素 6 周，显著降低了 TC、TGs 和 LDL-C 的水平，并降低了细胞间黏附分子-1 和簇状分化因子 68-细胞的浸润。在体外，通过将 CS 通过磷酸盐缓冲盐水鼓泡来制备 CS 提取物，以时间和浓度依赖的方式降低 HepG2 细胞中的 LDLR 表达，而用 100μM 褪黑素预处理可以预防这种作用。
总之，CS 暴露会损害肝细胞中的脂质代谢和 LDLR 表达，而褪黑素的补充可以预防这些影响。这些发现表明褪黑素在预防吸烟者脂质代谢紊乱方面具有潜在的治疗应用价值。
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