二氢杨梅素改善非酒精性脂肪肝小鼠肝脏生物钟相关基因表达节律紊乱

马鑫; 时皎皎; 陈卡; 易龙; 朱俊东; 糜漫天

doi:10.16016/j.1000-5404.201805085

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二氢杨梅素改善非酒精性脂肪肝小鼠肝脏生物钟相关基因表达节律紊乱

基础医学 | 更新时间：2026-01-09

- 二氢杨梅素改善非酒精性脂肪肝小鼠肝脏生物钟相关基因表达节律紊乱
- Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in non-alcoholic fatty liver mice
- 第三军医大学学报 2018年40卷第21期页码：1956-1961
- 作者机构：
- 作者简介：
- 基金信息：
  
  全军后勤科研重大项目(AWS17J014)
- DOI：10.16016/j.1000-5404.201805085
  中图分类号：
- 收稿：2018-05-11，
  
  纸质出版：2018-11-15
- 稿件说明：
移动端阅览
马鑫, 时皎皎, 陈卡, 等. 二氢杨梅素改善非酒精性脂肪肝小鼠肝脏生物钟相关基因表达节律紊乱[J]. 第三军医大学学报, 2018,40(21):1956-1961.

Xin MA, Jiaojiao SHI, Ka CHEN, et al. Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in non-alcoholic fatty liver mice[J]. Journal of Third Military Medical University, 2018, 40(21): 1956-1961.
马鑫, 时皎皎, 陈卡, 等. 二氢杨梅素改善非酒精性脂肪肝小鼠肝脏生物钟相关基因表达节律紊乱[J]. 第三军医大学学报, 2018,40(21):1956-1961. DOI： 10.16016/j.1000-5404.201805085.

Xin MA, Jiaojiao SHI, Ka CHEN, et al. Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in non-alcoholic fatty liver mice[J]. Journal of Third Military Medical University, 2018, 40(21): 1956-1961. DOI： 10.16016/j.1000-5404.201805085.

摘要

Abstract

Objective

To investigate the possible role of circadian rhythm variation of hepatic clock-related genes in the improvement of hepatic lipid metabolism in high-fat diet (HFD)-induced mice after dihydromyricetin (DHM) treatment.

Methods

A total of 150 C57BL/6J male mice (6 weeks old) were randomly divided into normal diet group (CON)

HFD group and HFD+DHM treatment [100 mg/(kg·d)] group. After 12 weeks of intervention

the liver tissues of mice were stained with oil O red

and the liver triglyceride levels were detected. The hepatocytes of each group were extracted at ZT18 and ZT6 by a two-step perfusion method according to the Zeitgeber time (ZT0 represents the light time point at 8:00 am). The oxygen consumption rate (OCR) was detected immediately. The liver tissues were also harvested at ZT0

ZT4

ZT8

ZT12

ZT16 and ZT20

respectively. The mRNA and protein expression levels of hepatic clock-related genes

circadian locomotor output cycles kaput (CLOCK)

brain and muscle-arnt-like 1 (BMAL1)

and Period2 (PER2) were detected by real-time PCR and Western blot analysis.

Results

The HFD group presented dominant accumulation of fat droplets in the interstitial space after oil O red staining and increased triglyceride content in the liver tissues (

0.05)

and significantly reduced basic OCR and maximum respiratory OCR level at the ZT18 and ZT6 (

0.05) when compared with the CON group. HFD feeding led to significantly decreased expression of CLOKC and BMAL1 at mRNA and protein levels at ZT0

ZT4

ZT8 and ZT20

and to that of PER2 at ZT4

ZT8

ZT16 and ZT20 in liver tissues (

0.05). Furthermore

DHM treatment significantly inhibited HFD-induced fat accumulation and hepatic triglyceride elevation as well as the decreased levels of the basis OCR and maximal respiratory OCR at ZT18 and ZT6 in the hepatocyte

s (with that of ZT18 significantly higher than that of ZT6). Besides

it also significantly antagonized HFD-induced changes of mRNA and protein expression of CLOCK.

Conclusion

DHM partially reverses the rhythm disorder of the expression of liver clock-related genes in non-alcoholic fatty liver disease mice

and thereby improves hepatic lipid metabolism.

关键词

Keywords

references

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