Effect of Jiangtang Xiaozhi Tablet on Liver Circadian Clock-related Genes CLOCK， BMAL1， REV-ERBα， and REV-ERBβ in Mice with Metabolic Dysfunction-associated Fatty Liver Disease
10.13422/j.cnki.syfjx.20221844
- VernacularTitle:降糖消脂片对代谢相关脂肪性肝病小鼠肝脏生物钟相关基因CLOCK、BMAL1、REV-ERBα、REV-ERBβ的影响
- Author:
Xiaoxiao CHEN
1
;
Min HOU
1
;
Pan WANG
1
;
Junguo REN
1
;
Jianxun LIU
1
Author Information
1. Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine， Institute of Basic Medical Sciences， Xiyuan Hospital， China Academy of Chinese Medical Sciences， Beijing 100091， China
- Publication Type:Journal Article
- Keywords:
metabolic dysfunction-associated fatty liver disease;
Jiangtang Xiaozhi tablet;
circadian clock-related genes
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(18):20-29
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of Jiangtang Xiaozhi tablet （JTXZT） on metabolic dysfunction-associated fatty liver disease and to study the mechanism from the perspective of circadian clock-related genes such as circadian locomotor output cycles kaput （CLOCK）， brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 （BMAL1）， reverse-eritroblastosis receptor （REV-ERB）α and β. MethodA total of 50 male SPF C57BL/6J mice were randomized into normal group （n=10） and modeling group （n=40）. The normal group was fed with normal diet， and the modeling group with high-fat diet for 4 weeks. Then the model mice were randomly classified into model group， high-dose （12.5 g·kg-1） and low-dose （6.25 g·kg-1） Jiangtang Xiaozhi tablet groups， and orlistat group （70 mg·kg-1）， with 10 mice in each group. The normal group and model group received equivalent volume of distilled water （8 weeks）. Then， the body weight of mice was measured， and the content of serum triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） was determined with biochemical method. Serum content of free fatty acid （FFA） and leptin was detected by enzyme-linked immunosorbent assay （ELISA）. Pathological changes of liver tissue and epididymal adipose tissue were observed based on hematoxylin-eosin （HE） staining. Liver fibrosis was examined based on Masson's trichrome staining， and changes of lipids based on oil red O staining. The expression of CLOCK， BMAL1， REV-ERBα， and REV-ERBβ was detected by Western blot and immunohistochemistry assay. ResultCompared with the normal group， the model group had high content of TG， TC， LDL-C， HDL-C， AST， ALT， FFA， and leptin （P<0.05， P<0.01）， showed ballooning degeneration and focal microvesicular steatosis of liver cells， enlarged adipocytes， and inflammatory cell clusters and fibrous tissue hyperplasia， and displayed increased protein expression of sterol regulatory element binding protein （SREBP） 1 and peroxisome proliferators-activated receptor （PPAR）γ （P<0.01） and decreased protein expression of PPARα （P<0.05）， CLOCK， BMAL1， REV-ERBα and β （P<0.05， P<0.01）. Compared with the model group， JTXZT-H group down-regulated the content of TG， TC， LDL-C， HDL-C， AST， ALT， FFA， and leptin in mice （P<0.05， P<0.01）， and the JTXZT groups demonstrated reduction in the degree and range of ballooning degeneration of liver tissue， alleviation of the compression of hepatic sinusoidal tissue， unobvious inflammatory cell infiltration and fibrous tissue proliferation， reduction in the expression of SREBP1 and PPARγ （P<0.05， P<0.01）， and rise of the protein expression of PPARα （P<0.01）， CLOCK， BMAL1， REV-ERBα， and REV-ERBβ （P<0.05， P<0.01）. ConclusionJTXZT can significantly alleviate the metabolic dysfunction-associated fatty liver disease in mice caused by high-fat diet. The mechanism is the likelihood that it regulates downstream related lipid metabolism proteins （such as SREBP1， PPARγ， and PPARα）.
