长期睡眠期噪声暴露对肝脏生物钟及脂代谢的影响

张鑫垚; 佘晓俊; 付一鸣; 付波; 王硕; 程梦竹; 王瑞; 崔博

doi:10.11836/JEOM23189

长期睡眠期噪声暴露对肝脏生物钟及脂代谢的影响

Effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism

摘要

摘要:
背景长期睡眠期噪声可能对代谢系统产生不利影响，肝脏脂质代谢与生物钟基因关系密切。
目的探讨长期睡眠期噪声暴露对小鼠肝脏生物钟及脂质代谢的影响及相关机制。
方法 20只C57BL/6J 雄性小鼠随机分为噪声暴露组和对照组，每组10只。噪声暴露组小鼠连续30 d暴露于白噪声90 dB声压级（SPL），每天8 h，从9：00—17：00。对照组背景噪声≤40 dB SPL。噪声暴露结束后在14：00（ZT6）和2：00（ZT18）处死动物，每个时间点处死5只，收集肝脏组织。采用胆固醇氧化酶法和磷酸甘油氧化酶法测定肝脏总胆固醇、甘油三酯。实时荧光定量PCR法检测肝脏内生物钟基因Clock、Bmal1、Rev-erbα、Rev-erbβ，以及脂质代谢基因Srebp1c、Hmgcr、Fasn、Lxrα、Acc1、Chrebp的表达。
结果在ZT18时，噪声暴露组小鼠肝脏总胆固醇含量较对照组升高48%（P<0.05），甘油三酯含量升高61%（P<0.05）。与对照组相比，噪声暴露组小鼠肝脏内的生物钟基因Clock、Bmal1 mRNA的表达在ZT18时升高（P<0.05），在ZT6时降低（P<0.05）；Rev-erbα mRNA表达水平在ZT6、ZT18时均降低（P<0.05）；Rev-erbβ mRNA表达水平则在ZT6、ZT18时均无明显变化。噪声暴露组小鼠肝脏脂质代谢相关基因Srebp1c、Hmgcr、Chrebp、Lxrα mRNA的表达较对照组在ZT18时均升高（P<0.05）；Acc1、Fasn mRNA的表达在ZT6时无明显变化，在ZT18时则均有上升的趋势，但结果差异尚无统计学意义（P>0.05）。
结论长期睡眠期噪声暴露可致小鼠生物钟及脂代谢紊乱。噪声暴露抑制关键生物钟基因Rev-erbα的表达，使脂质合成基因Srebp1c和Chrebp上调，促进肝脏脂质沉积，导致脂质代谢紊乱。

Abstract:
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, suppression 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.

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