Zhu Zhu, Hua Bingxuan, Shang Zhanxian, Yuan Gongsheng, Xu Lirong, Li Ermin, Li Xiaobo, Sun Ning, Yan Zuoqin, Qian Ruizhe, Lu Chao
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Biomed Res Int. 2016;2016:5438589. doi: 10.1155/2016/5438589. Epub 2016 Aug 18.
Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.
背景。在脂质代谢异常和昼夜节律紊乱的情况下，动脉粥样硬化的风险会升高。我们研究了异常光照条件是否会影响载脂蛋白E基因敲除（ApoE-KO）小鼠中生物钟基因以及生物钟调控的脂质代谢相关基因的昼夜表达。方法。通过改变光照暴露，利用ApoE-KO小鼠（ApoE-KO LD/DL小鼠）建立了一种伴有生物钟基因表达紊乱的动脉粥样硬化小鼠模型。将暴露于正常昼夜节律和正常饮食的C57 BL/6J小鼠（C57小鼠）和ApoE-KO小鼠（ApoE-KO小鼠）作为对照小鼠。根据授时因子时间采集样本，以检测动脉粥样斑块的形成、血脂水平及其节律性、生物钟基因、脂质代谢相关基因以及沉默调节蛋白1（Sirt1）的水平及其节律性。结果。ApoE-KO LD/DL小鼠的主动脉弓形成了动脉粥样硬化斑块。与对照小鼠相比，ApoE-KO LD/DL小鼠的血脂水平及其波动发生了改变，同时生物钟基因、脂质代谢相关基因以及Sirt1的水平和昼夜波动也发生了变化。结论。异常光照暴露加剧了斑块形成，加重了血脂、生物钟基因、脂质代谢基因以及Sirt1水平的紊乱和昼夜节律振荡。
