Effect of <italic style="font-style: italic">Shuxie Decoction</italic> （疏泄方） on Hepatic Lipid Accumulation and Bmal1 Clock Gene Expression  Circadian Rhythm Disorders Model Mice

ZHANG Mengting; HUANG Ting; LIU Xinyan; LI Jing; WU Wanhong; HUANG Caoxin; CAI Teng; WANG Mengyuan; ZHAO Nengjiang; LIU Suhuan; YANG Shuyu

doi:10.13288/j.11-2166/r.2025.18.013

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Effect of Shuxie Decoction （疏泄方） on Hepatic Lipid Accumulation and Bmal1 Clock Gene Expression Circadian Rhythm Disorders Model Mice

更新时间：2025-09-12

- Effect of Shuxie Decoction （疏泄方） on Hepatic Lipid Accumulation and Bmal1 Clock Gene Expression Circadian Rhythm Disorders Model Mice
- Journal of Traditional Chinese Medicine Vol. 66, Issue 18, Pages: 1934-1943(2025)
- 作者机构：
  
  1.福建中医药大学中医学院，福建省福州市闽侯县上街镇邱阳路1号，350122
  2.厦门大学附属第一医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.18.013
  CLC：
- Received：17 April 2025，
  
  Revised：2025-07-15，
  
  Published：17 September 2025
- 稿件说明：
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张梦婷,黄婷,刘欣妍等.疏泄方对昼夜节律紊乱模型小鼠肝脏脂质堆积及生物钟基因Bmal1表达的影响[J].中医杂志,2025,66(18):1934-1943.

ZHANG Mengting,HUANG Ting,LIU Xinyan,et al.Effect of Shuxie Decoction （疏泄方） on Hepatic Lipid Accumulation and Bmal1 Clock Gene Expression Circadian Rhythm Disorders Model Mice[J].Journal of Traditional Chinese Medicine,2025,66(18):1934-1943.
张梦婷,黄婷,刘欣妍等.疏泄方对昼夜节律紊乱模型小鼠肝脏脂质堆积及生物钟基因Bmal1表达的影响[J].中医杂志,2025,66(18):1934-1943. DOI： 10.13288/j.11-2166/r.2025.18.013.

ZHANG Mengting,HUANG Ting,LIU Xinyan,et al.Effect of Shuxie Decoction （疏泄方） on Hepatic Lipid Accumulation and Bmal1 Clock Gene Expression Circadian Rhythm Disorders Model Mice[J].Journal of Traditional Chinese Medicine,2025,66(18):1934-1943. DOI： 10.13288/j.11-2166/r.2025.18.013.

摘要

目的

探讨疏泄方改善昼夜节律紊乱引起肝脂质堆积的可能作用机制。

方法

240只C57BL/6小鼠随机分为对照组、模型组、疏泄方低剂量组、疏泄方高剂量组和阿戈美拉汀组，每组48只。除对照组外，其余各组小鼠采用光剥夺方式建立昼夜节律紊乱模型小鼠。造模2周后疏泄方低、高剂量组小鼠每10 g体质量分别给予疏泄方0.15、0.31 g/d灌胃，阿戈美拉汀组小鼠每10 g体质量给予阿戈美拉汀片0.03 mg/d灌胃，对照组和模型组小鼠每10 g体质量给予0.1 ml/d蒸馏水灌胃，各组均每天灌胃1次，共灌胃2周。最后一次给药次日，采用跑轮实验观察小鼠日间（8：00—20：00）和夜间（20：01—8：00

）转数总和；采用代谢笼记录小鼠24 h不同时间［北京时间11：00（ZT3）、15：00（ZT7）、19：00（ZT11）、23：00（ZT15）、3：00

（ZT19）、7：00

（ZT23）］摄食量；比色法检测不同时间各组小鼠肝脏甘油三酯（TG）水平；HE染色法观察肝组织病理形态；免疫荧光法检测围脂滴蛋白1（perilipin1）免疫荧光密度；RT-qPCR和Western Blot法分别检测脑和肌肉芳香烃受体核转运蛋白样蛋白1（Bmal1）、过氧化物酶体增殖物激活受体γ共激活因子1a（

PGC

）mRNA表达和蛋白水平。

结果

对照组、疏泄方低剂量

组和阿戈美拉汀组夜间跑轮转数总和较本组日间显著升高（

＜0.01）；与对照组同时间比较，模型组小鼠日间跑轮转数总和显著增加（

＜0.01）；与模型组同时间比较，疏泄方低剂量组和阿戈美拉汀组日间跑轮转数总和显著降低，疏泄方低剂量组在ZT7时摄食量显著减少（

＜0.05）。肝脏病理结果显示，对照组、阿戈美拉汀组及疏泄方低、高剂量组小鼠肝细胞形态规则，而模型组小鼠肝细胞排列紊乱、少量空泡状细胞。与对照组同时间比较，模型组ZT11和ZT15时TG含量显著升高，ZT15时肝脏组织perilipin1蛋白免疫荧光密度增强，

Bmal1

mRNA表达量在ZT3、ZT7显著升高，Bmal1蛋白及其mRNA在ZT15时显著降低，ZT11时

PGC

mRNA表达及其蛋白水平降低，ZT15时

PGC

mRNA表达及其蛋白水平升高（

＜0.05或

＜0.01）。与模型组同时间比较，ZT15时疏泄方低剂量组及阿戈美拉汀组TG含量降低；疏泄方低、高剂量组perilipin1蛋白免疫荧光密度减弱；疏泄方低剂量组在ZT7时

Bmal1

mRNA表达量降低，Bmal1蛋白水平在ZT3、ZT11和ZT15时均升高，ZT11时

PGC

mRNA表达及其蛋白水平升高，ZT15时

PGC

mRNA表达及其蛋白水平降低（

＜0.05或

＜0.01）。

结论

低剂量疏泄方可调控昼夜节律紊乱，改善肝脏脂质堆积，其机制可能通过有效调节肝脏

Bmal1

、

PGC

mRNA表达及蛋白水平发挥降低肝TG的作用有关。

Abstract

Objective

To explore the potential mechanism of

Shuxie Decoction

（疏泄方） in alleviating hepatic lipid accumulation caused by circadian rhythm disorders （CRD）.

Methods

Totally 240 C57BL/6 mice were randomly divided into control group， model group， low-dose

Shuxie Decoction

group， high-dose

Shuxie Decoction

group， and agomelatine （Ago） group， with 48 mice in each group. Except for the control group， mice models of CRD were established by light deprivation. Two weeks after modeling， mice in low- and high-dose

Shuxie Decoction

groups groups were treated with 0.15 and 0.31 g/day of

Shuxie Decoction

per 10 g of body weight via oral gavage， respectively； mice in Ago group were given 0.03 mg/day of agomelatine tablets per 10 g of body weight via oral gavage； while mice in the control group and the model group wer

e given 0.1 ml/day of distilled water per 10 g of body weight by intragastric administration. All groups were administered once daily for a total of 2 weeks. On the day after the last administration， the total number of wheel rotations during the daytime （8：00-20：00） and nighttime （20：01-8：00

） was observed using a running wheel experiment； metabolic cages were used to record food intake at 11：00 （ZT3）， 15：00 （ZT7）， 19：00 （ZT11）， 23：00 （ZT15）， 3：00

（ZT19）， and 7：00

（ZT23） Beijing Time； colorimetric assay was used to measure triglyceride （TG） levels in liver tissue at different time points across groups； Hematoxylin

Eosin （H

E） Staining was used to examine liver tissue pathology； immunofluorescence assay was used to measure the immunofluorescence density of perilipin 1 （PLIN1）； RT-qPCR and Western Blot assays was used to measure the mRNA expression and protein levels of brain and muscle aromatic hydrocarbon receptor nuclear translocator-like protein 1 （Bmal1） and peroxisome proliferator-activated receptor gamma coactivator 1a （PGC-1α） in brain and muscle tissues.

Results

The total number of nighttime wheel rotations in the control group， the low-dose

Shuxie Decoction

group and Ago group were significantly higher than that in the daytime of the same group （

＜0.01）； compared with the control group at the same time point， the total number of daytime wheel rotations in the model group was significantly increased （

＜0.01）； compared with the model group at the same time point， the total number of daytime wheel rotations in low-dose

Shuxie Decoction

group and Ago group significantly reduced， and low-dose

Shuxie Decoction

group showed a significant decrease in food intake at ZT7 （

＜0.05）. The liver pathology results showed that the liver cells of mice in control group， Ago group， low- and high-dose

Shuxie Decoction

groups ha

d regular morphology， while the model group had disordered liver cell arrangement and a small number of vacuolar cells. Compared with the control group at the same time points， TG levels in the model group significantly elevated at ZT11 and ZT15， the immunofluorescence density of perilipin1 protein in liver tissue enhanced at ZT15，

Bmal1

mRNA expression significantly elevated at ZT3 and ZT7， Bmal1 protein and its mRNA levels significantly reduced at ZT15， and

PGC

1α

mRNA expression and its protein levels decreased at ZT11 but increased at ZT15 （

＜0.05 or

＜0.01）. Compared with the model group at the same time point， TG levels were reduced in low-dose

Shuxie Decoction

group and Ago group at ZT15； the immunofluorescence density of perilipin1 protein was weakened in low- and high-dose

Shuxie Decoction

groups； in low-dose

Shuxie Decoction

group，

Bmal1

mRNA expression decreased at ZT7， while Bmal1 protein levels increased at ZT3， ZT11， and ZT15， while

PGC

1α

mRNA expression and its protein levels increased at ZT11， and

PGC

1α

mRNA expression and its protein levels decreased at ZT15 （

＜0.05 or

＜0.01）.

Conclusion

Low-dose

Shuxie Decoction

can regulate circadian rhythm disorders and improve hepatic lipid accumulation. The mechanism may be related to the reduction of hepatic triglycerides through the upregulation of hepatic Bmal1 and PGC-1a levels.

关键词

Keywords

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Effect of Shuxie Decoction （疏泄方） on Hepatic Lipid Accumulation and Bmal1 Clock Gene Expression Circadian Rhythm Disorders Model Mice

DOI：10.13288/j.11-2166/r.2025.18.013

摘要

Abstract

关键词

Keywords

references