长期睡眠期噪声暴露对肝脏生物钟及脂代谢的影响OA

[Background]Long-term exposure to noise during sleep may has adverse effects on metabolic system,and liver lipid metabolism is closely related to circadian clock genes. [Objective]To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. [Methods]Twenty C57BL/6J male mice were randomly divided into two groups:a noise exposure group and a control group with 10 mice in each group.The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level(SPL)for 30 consecutive days,8 h a day,from 9:00 to 17:00.The mice in the control group were exposed to background noise≤40 dB SPL.After noise exposure,the animals were neutralized at 14:00(ZT6)and 2:00(ZT18),5 animals at each time spot,and the liver tissues were collected.Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively.The expressions of circadian clock genes(Clock,Bmal1,Rev-erbα,and Rev-erbβ)and lipid metabolism genes(Srebp1c,Hmgcr,Fasn,Lxrα,Acc1,and Chrebp)in liver were detected by quantitative real-time PCR. [Results]Compared with the control group,the content of total cholesterol in liver in the noise exposure group increased by 48%(P<0.05)and the content of liver triglyceride increased by 61%(P<0.05)at ZT18.The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6(P<0.05).The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18(P<0.05).The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18.The mRNA expression levels of liver lipid metabolism related genes Srebp1c,Hmgcr,Chrebp,and Lxrα in the noise exposure group were higher than those in the control group at ZT18(P<0.05).The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6,then an upward trend at ZT18,but no significant difference between the two time spots(P>0.05). [Conclusion]Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice.Among them,sup-pression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver,resulting in lipid metabolism disorder.